The back issues
Long before complex life arose, bacteria had mastered the art of living. To survive, these single-celled organisms learned how to divide, with one cell giving rise to two, then two to four, and so on. It was a survival strategy that turned out to be so convenient that it was adopted, and has evolved over billions of years. Decades of research have been put into understanding bacterial division. As it turns out, it is not a one-man show but takes the well-coordinated and timely appearance of several proteins to orchestrate the transformation of one cell into two. And it all starts with a protein called FtsZ, which is at the heart of a sort of scaffold that will ultimately allow a cell to divide into two.
Protein(s): Cell division protein FtsZ
It is important to know when to stop. A cell has to know when to stop expanding. A flower's pistil and its stamen when to stop elongating. And a flagellum to stop extending. Because there is a fair chance that without this knowledge, it would be difficult to keep organisms alive. But how do all these various parts of living matter know when the time has come to stop growing? There must be a mechanism of some kind. A sort of molecular device which holds up a STOP sign, or acts as a means of measure when something has reached the required shape or length. Recently, such a scheme was discovered in the flagella of the alga Chlamydomonas reinhardtii; a ruler of sorts that defines not only the length of the units which make up the axoneme but also the nature of the flagellum's structure. This molecular yardstick is a protein known as coiled-coil domain-containing protein 40 - or CCDC40.
Protein(s): Coiled-coil domain-containing protein 40 homolog
There is more to red than meets the eye. The colour has probably been around for as long as plants have, spreading red across stalks, leaves, fruits and flowers to seduce the incidental pollinator or ward off predators. Surprisingly, although Nature usually tends towards the most economical, in plants there are two ways of making red by using either of two biosynthetic pathways: the betalain one, or the anthocyanin one. While the anthocyanin pathway only produces reds, the betalain pathway supplies both red and yellow pigments. But anthocyanins and betalains are never synthesized within the same plant; it is one or the other. This probably has to do with evolution and the choice of favouring one pathway over another. One protein which has a key role in triggering off the betalain pathway has recently been revealed - transcription factor MYB1.
Protein(s): Transcription factor MYB1
Paradigms are meant to be broken. In the 1980s, biology students were taught "the one gene = one protein" dogma which has since stepped down from its pedestal, as we now know that one gene, by way of any number of post-translational modifications on the protein sequence, can actually give rise to more than one protein. Or what would be more correct: to more than one function. In the same way, structural biologists are beginning to realise that proteins are not always stable but that a significant amount exist in particularly unstable forms - which has given them the name "disordered proteins". Until recently, proteins were thought to fold up into thermodynamically stable forms before getting on with what they had to do. Now we know that it is not necessarily the case. Eukaryotic translation initiation factor 4E-binding protein 2, for instance, is one such disordered protein whose lack of stability gives rise to a new kind of biological regulation.
Protein(s): Eurkaryotic translation initiation factor 4E-binding protein 2
Some mistakes turn out to be beneficial. And life, or its survival, has always thrived on them. Add a few mutations to a genome, drench it in time, and you have the driving force of evolution. Transposons - these bits of DNA that are able to skip along genomes - are just one kind of mutation that has contributed hugely towards life's unfolding. Not so long ago, researchers discovered remnants of a well-known transposon, made up of so-called mariner elements, glued aside another gene whose product is a histone methyltransferase. This chimeric gene, baptised SETMAR, expresses a product whose roles are similar to both of its parts. But with a little twist. A twist which, in the past 50 million years, has contributed to human evolution, and is due to the protein it expresses: histone-lysine N-methyltransferase SETMAR.
Protein(s): Histone-lysine N-methyltransferase SETMAR
Nature has its secret ways. During the course of the 19th century, the Augustinian friar Gregor Mendel worked out the basics of genetic inheritance as he crossbred pea plants. About a century later, it has become obvious that the inheritance of a given trait is in fact not so straightforward. What is more, there seems to be growing evidence that a given trait can actually be handed down generations - even skipping generations - without it being frankly dictated by a gene; a notion which, in the realm of biological dogmas, is like a crack at the base of a sturdy building. The concept is not really new but scientists may have strengthened it following studies on folate metabolism - one of whose major protagonists is methionine synthase reductase, or Mtrr - by suggesting a mechanism of inheritance that is driven by entities which are not an actual part of a gene, otherwise known as epigenetic inheritance.
Protein(s): Methionine synthase reductase
There is no life without a heart. And none without a beat. Which is why the heart is one of the first organs to be formed - albeit in a rudimentary fashion - very early on in life; as early as two weeks in the human embryo which, at that point, bears little resemblance to a human being. The heart is such a vital part of us that it has been a symbol of life for millennia, as it has of love, because so many of our emotions pass through it, either making it flutter, skip a beat or beat faster. It is so central that a lot of time, thought and energy is put into keeping a heart pulsing, be it during an operation or following cardiac arrest. Some hearts are also born lazy, which can be seriously disabling. Pacemakers are an answer to this, but they are artificial so have their drawbacks. A biological alternative, however, known as T-box transcription factor Tbx18, could prove to be revolutionary in the near future.
Protein(s): T-box transcription factor Tbx18
Nature's imagination seems endless, and so is Man's. For as long as humans have existed, they have twisted Nature to meet their own needs. Wood has been used to keep them warm. Whale oil has been used to make light. Water has been harnessed to make electricity. And when the era of bio-engineering developed, it was not long before scientists found ways to tinker with an organism's genome for the benefits of mankind. Nowadays, the realm of medication depends heavily on biotechnology. And so, undoubtedly, will novel biofuels. With fossil fuels slowly trickling away, it is becoming paramount to find alternative sources of fuel. And ethanol, though not a new idea, is one. Ethanol is synthesized quite naturally by microorganisms - usually as a waste product - and is the result of the degradation of sugars, by an enzyme known as inulinase, and their subsequent fermentation.
Protein(s): endo-inulinase inuA
Pairing up is sometimes paramount to life. On the molecular scale, dimerization in our bodies is at the heart of many fundamental biological processes, such as the transduction of signals from the outside of a cell to the inside for instance. Split two molecules apart and, just like taking the propeller away from a ship, things are sure to change drastically. Signal transduction, on which life depends, is hugely due to protein-protein interaction. A ligand recognises its receptor, binds to it, thereby triggering off biological processes downstream. In the case of Kit ligand, and its receptor Kit, their binding is subject to the dimerization of both the ligand and its receptor, following which signals are transduced further downstream triggering off other biological processes. Kit ligand and Kit are a case of substantial conformational change on the molecular level - dimerization but also angles which bring about flexibility - that are necessary for Kit to get on with its job.
Protein(s): Kit ligand, Kit
Temperatures can get cold. And living organisms have to find ways of keeping themselves warm. Humans use clothes. Polar bears grow fur. Whales are lined with blubber. And many animals avoid the cold by migrating to warmer parts of the planet. But for cold-blooded animals - such as fish - things are sometimes more complicated. Especially when they live in waters which are ice-cold, on a seasonal basis or not. The formation of ice in an organism is dangerous because it can damage cells irreversibly. To solve this problem, Nature thought up an antifreeze system which hinders ice formation: antifreeze proteins. There are all sorts of antifreeze proteins but one is particularly special - Maxi - and keeps fish alive in waters as cold as - 1.9 °C. As its name suggests, it is much larger than the other antifreeze proteins known to date, but it also behaves very differently. What is more, its 3D structure has shed a very different light on the way the core of a protein is formed.
Protein(s): Antifreeze protein Maxi
Life is made of smells. Because smells play an important part in an organism's ordinary day to day life - it's a question of survival. And who says survival, says reproduction and food. Flowers exude perfumes to attract pollinators. There is evidence that spermatozoa sniff their way to eggs. Animals avoid eating what smells bad, but will be seduced by what smells good. While others let off putrid scents to ward off predators or, on the contrary, discharge encouraging ones to lure their prey. On the whole, the process is simple. If a fragrance is pleasant, an organism will be attracted by it. If it is not, it will turn away. This relatively direct means of communication between organisms is carried out by a more or less elaborate olfactory system. Recently, scientists managed to modify an odorant receptor - known as Orco - of Aedes aegypti, the mosquito responsible for transmitting yellow fever and dengue fever to humans. In so doing, the mosquito seemed to lose its taste for human skin - a valuable fact which could be used to develop powerful insect repellents.
Protein(s): Odorant receptor coreceptor
What is new to us is not necessarily new to Nature. There are things that have been around for years, even millions of years, which have remained hidden to scientists because they lacked the knowledge to unveil them. The methane you find in oceans - a portion of which ends up in the atmosphere - is one of Nature's riddles. The methane content of the ocean is substantial and, according to researchers, cannot have only been synthesized by the anaerobic archaea who live in its depths. Especially since deep-ocean methane can take a long time to percolate from its original source to the shallower parts of the sea. So what else could be making methane in these waters? Well recently, biologists discovered that a marine microbe living closer to the surface of the ocean, and known as Nitrosopumilus maritimus, feeds on a very unusual chemical compound - HEP - and, in the process, releases methane. And, since the ocean is bulging with these microbes, this could very well account for a lot of the methane that is found in it. Shortly after this revelation, scientists discovered the enzyme that converts this particular compound, which they baptised methylphophonate synthase.
Protein(s): Methylphosphonate synthase
The life sciences owe a lot to green peas. And perhaps even to the bishop of St Thomas Abbey in Brno - now the Czech Republic. It was there, in the 1850s, that Gregor Johann Mendel (1822-1884) decided to undertake studies on heredity using mice. The bishop, however, disagreed with research involving animal sex, so his friar turned to the more innocent garden pea. Mendel spent the best part of a decade cross-breeding peas, while considering seven different phenotypic traits that seemed - to him - to be inherited independently: stem length, pod shape, pod colour, seed shape, flower colour, flower location and plant height. Little did he know that the results he so painstakingly jotted down, and which were published in 1866, would bring about a small revolution in the world of biology - although only in the first quarter of the 20th century.
Protein(s): Basic helix-loop-helix protein A, Gibberellin 3-beta-dioxygenase 1, Starch branching enzyme I, Protein STAY-GREEN
Many of our cells are not...us... Besides the cells we produce, we carry around an awful lot of bacteria. In reality, 90 percent of the cells that make us up are bacterial, that is to say about one billion billion. That's a lot. A large proportion of these bacteria are part of our gut, add an average of 2 kg to our adult weight and form what has been termed our gut microbiome. Why have they set up camp inside us? Because we need them... And vice versa. The human gut hosts bacteria that are able to break down all sorts of molecules we cannot. In exchange, we offer them an environment to thrive in. This mutual parasitism has evolved over time, and is a consequence of the various surroundings humans have lived in, especially the kinds of food we have eaten, and eat. Recently, scientists discovered that a group of Japanese were able to digest polysaccharides westerners are unable to. It turned out that this was most probably the result of the long Japanese tradition of eating 'nori', an edible seaweed species of the red algae, and is due to specific seaweed carbohydrate active enzymes which have become an integral part of their digestive system.
Protein(s): Beta-porphyranase B, Beta-porphyranase A, Beta-agarase
Pain is part of an animal's life. It is there to tell us that something is wrong, and needs to be attended to. There is moral pain. And physical pain, the more definable of the two, which serves two purposes. The first, to warn us of tissue damage and, more often than not, its localisation. The second, to understand where danger lies, so as to avoid it in the future. Unless, of course, it has been lethal. Ever since Life emerged, Nature has been using pain as a means of communication. Though perhaps violent, it is usually very conclusive, which is why many animals have developed toxins they inject into potential predators to ward them off. Among these toxins are the well-known venom cocktails snakes, scorpions and spiders are able to conjure up. In answer to this, a few animals have developed mechanisms to ease the pain - or even suppress it altogether. This is the case of one species of mouse - the Southern grasshopper mouse from the Texan desert - who feels next to no pain when stung by the bark scorpion. As a consequence, the mouse is able to ignore the sting and eat the scorpion. Recent studies have demonstrated that this extraordinary ability is due to changes in the structure of a given type of pore: sodium channel protein type 10 subunit alpha, or Nav1.8.
Protein(s): Sodium channel protein type 10 subunit alpha
I have been writing up articles for Protein Spotlight for the past 13 years, doing my best to inject both a human touch and a little bit of art into each one. Earlier this month, I received for the very first time, something with just this mixture from a scientist who had been inspired by one of my recent articles - On Sex, Drugs and Satisfaction - all about neuropeptide F, the lack of sex and Drosophila melanogaster who is prone to turn to the benefits of alcohol if the act of mating has been denied him...
Protein(s): Neuropeptide F
Life depends on exchange. To this end, and on the cellular level, molecules are continuously secreted for the purposes of signalling, strengthening, transporting, protecting... Sometimes, the primary role of a molecule can bring about an unforeseen consequence which - if positive - is gladly preserved for the benefit of the species. This seems to be the case for a particular form of a polysaccharide known as hyaluronan: high molecular mass hyaluronan, or HMM-HA. The polymer is secreted in large quantities in a rather peculiar animal - the naked mole rat, or Heterocephalus glaber - and is thought to be responsible, at least in part, for the animal's exceptionally long life span, because of the total absence of any form of cancer. Consequently, understanding how HMM-HA achieves this - and particularly the enzyme which synthesizes it, hyaluronan synthase 2 - could pave the way to therapies able to fight off the formation of malignant tumours.
Protein(s): Hyaluronan synthase 2
Never take a walk for granted. Putting one leg in front of the other is not a simple affair. To most of us, it seems so easy. Yet walking - and its faster version, running - demands intricate neuron development and networking that is gradually set in place during the course of embryogenesis and very early childhood. Walking can be learned, as long as you have the correct bases to begin with. Watch a toddler taking its first steps. They lose balance. Cave in. Fall. But, within a few weeks, a small human - although far slower than most vertebrates - manages to master the technique of standing up and moving forward by using its two legs very successfully. The art of walking, or locomotion, demands close coordination between left, right, forward and backwards, as well as the limbs' muscles - without which walking would be a difficult enterprise*. In the case of four-legged vertebrates, coordination is even more complex. Recently, Swedish scientists discovered a protein - the Duplex and Mab-3 related Transcription Factor - which is directly involved in a horse's gait, and gives an insight into how locomotion, as a whole, is managed and organised both on the cellular and molecular level.
Protein(s): Doublesex- and mab-3-related transcription factor 3
There is no life without water. However, living beings go through life with given amounts of water inside them. Which is why there has to be a system that sustains this balance, and prevents too much water from flowing in, or indeed pouring out. Too large a volume of water in an organism, or too small a one, brings about serious deficiencies, which can lead to an organism's death. So Nature devised a water barrier which it built around all its creations - a sort of seal that makes sure the volume of water we carry within us remains as stable as possible. When this barrier is deficient, though, individuals can suffer from skin disorders known as ichthyosis - or dry skin - to varying degrees: some mild, others lethal. Since the 1920s, it has been known that fatty acids have a role in mammalian skin hydration. Recently, researchers discovered how two lipooxygenases - epidermis-type lipoxygenase 3 and 12 - have a crucial role in the construction of the mammalian water barrier - and hence our aqueous well-being - thanks to their interactions with essential fatty acids.
Protein(s): Arachidonate 12-lipoxygenase 12R-type, Hydroperoxide isomerase ALOXE3
All vertebrates have a skull. In which is lodged - and protected - one of the most important and complex biological tissues that exists, i.e. the brain tissue. When you compare the brains of different animals, there is one thing that stands out immediately: the amount of folds. The brain of a marmoset or mouse, for instance, seems almost smooth when put beside a sheep's, or a human's. It all has to do with available space. Human brain tissue presents such a large surface that the only way Nature has found to fit it into a rather small receptacle is to fold it many times - very much like inserting a large blanket into a small drawer. This folding has given the human brain the particular architectural characteristics it has; an architecture which - when altered - can cause severe neurological harm. Recently, scientists discovered a protein which has a direct role in folding brain tissue during brain development: TMF-regulated nuclear protein 1, or Trnp1.
Protein(s): TMF-regulated nuclear protein 1
There is not one living being on earth that doesn't need to eat. And we all go about it in the most ingenious ways. Humans go hunting in supermarkets. Dogs wait for food to appear in their bowls. Mosquitoes suck blood. Plants seep in light. Frogs await the passing fly. There are, however, organisms that go one step further in their quest for food, and that is to use another living being to produce what they need to eat. This is the realm of parasitism, some forms of which are particularly inventive. In this respect, one nematode, known as the soybean cyst nematode worm - or Heterodera glycines - is capable of taking advantage of soybean roots and modifying parts of them to erect the ideal feeding place. They do this by injecting effector proteins into the plant, a few of which are able to mimic plant proteins involved in plant development. These particular nematode proteins are known as CLE-related proteins and represent a very subtle way of twisting a host's welcome to their advantage.
Protein(s): CLE-related protein 1, CLE-related protein 2
We all need a nose. Inside this part of an animal's body lie millions of olfactory receptors awaiting smells that they will send on to the brain. In turn, our brain will say whether the smell is good, or bad - a simple way of informing an animal of what could be potentially harmful for it or, on the contrary, beneficial. The mechanism is pretty straightforward and has evolved over time to give the best chances of survival to living species. As for humans, their olfactory capacities are naturally far less fine-tuned than a dog's or a wild animal's, but they remain essential nevertheless. We are still very much aware of smells that spell 'not good' or 'lovely', and react accordingly. For years, researchers have wondered whether the actual perception of a smell has a genetic basis. Much has already been written on the subject, and the answer seems to be 'yes'. Recently, scientists discovered that the perception of the characteristic smell of cut grass has a genetic basis, and is probably under the influence of an olfactory receptor dubbed 'olfactory receptor 2J3', or OR2J3.
Protein(s): Olfactory receptor 2J3
There is no life without smells. In the wild, smells - and the capacity to sense them - are the basis for survival for plants and animals. They are used to attract, seduce, repel or protect, and are with us night and day; so much so that life would seem very bland without them. On the whole, for any given species, a pleasant perfume implies that all is well, while a bad one suggests that something is wrong. The smells the human body gives off are a combination of who we are, what we eat, and the general state of certain metabolic cycles. When part of a metabolic cycle is deficient, a change in our bodily odours can occur. This is the unfortunate case of what is known as the 'fish odour syndrome', or trimethylaminuria. People afflicted with trimethylaminuria release a smell of rotting fish. The symptoms were first clinically described in the 1970s and, in the 1990s, scientists discovered the cause: a malfunction of an enzyme known as flavin-containing monooxygenase 3.
Protein(s): Dimethylaniline monooxygenase [N-oxide-forming] 3
Humans have always sought to make life sweeter. In prehistoric times, sugar cane was already being grown for its sweetening powers, and the sugar added to beverages and food. But why do humans like what is sweet so much? This may well have evolved from our distant ancestors, as far back as those who bore little resemblance to us. In the wild, animals have to depend on colour but also taste - and its very close sister, smell - to distinguish what is edible from what is likely to be toxic. On the whole, bitter is better left alone. As things evolved, a sweet taste became a feeling that was comforting one way or another. So, slowly but surely, sweetness was added to all sorts of foods and liquids. And, today, sugar is usually part of a Westerner's diet - whether we are aware of it or not. As a result, towards the end of the 20th century, it had become clear that sugar - or an excess of it - was proving to be harmful to the human population, and it was necessary to find ways of making life sweeter without the nasty side effects. In the early 1980s, one such sweetener was rediscovered in a South American plant, Lippia dulcis. Known as Hernandulcin, researchers have recently managed to isolate a key enzyme in its synthesis, known as (+)-epi-alpha-bisabolol synthase.
Protein(s): (+)-epi-alpha-bisabolol synthase
There can be little worse than seeing - and feeling - your own child retreat into a world that doesn't involve yours. Especially at a period of life when contact with a mother and a father is such a vital component of an infant's development. And such a pleasurable one for the parents. Autism hits about one child in a thousand - although the contours of the affliction remain a little hazy. There are many forms. Some more serious than others. Some widespread while others are rare, or even unique. The common denominator is what could be described as a characteristic aloneness, where those suffering from autism are unable to interact socially and communicate in the way most of us do. Today, researchers believe that autism has a strong genetic component and that certain mutations are at the heart of autistic behaviour. One such mutation affects an enzyme known as BCKDK and may well be responsible for a rare hereditary form of autism that could be treated with a specific diet.
We all need guidance in life. And sperm cells are no exception to the rule. In plants, as in all living beings that depend on sex to multiply, a male gamete has to reach a female gamete in order to fuse with it. All sorts of mechanisms are used for this to occur. And plants are among the most imaginative organisms on the planet, simply because their mobility is so reduced. As such, they depend on forms of mobility that surround them: wind, bees, wild animals... And they have exploited this remarkably. At the molecular level, however, plants are far more mobile. An example is pollen tube elongation. In mouse-ear cress (Arabidopsis thaliana), for instance, once the pollen is ready to germinate, a bulge protrudes from its surface, elongates - and forms what is known as the pollen tube. Hordes of molecules are involved in pollen tube elongation. But you also need something which can actually guide the tube towards the ovule. And its name is protein HAPLESS 2, or HAP2.
Protein(s): Protein HAPLESS 2
Sex for procreation. It doesn't sound in the least bit eccentric. But how about sex between a flower and an insect? We all know that flowers depend very much on insects to perpetuate their species. It is their answer to a lack of legs or wings. Consequently, over the millennia, plants have devised the most creative ways of luring insects into the places where they keep pollen. Some flowers have thought up shapes that resemble an insect's mate, or places that are ideal for shelter, or they cunningly display colours that are hard for the six-legged species to ignore. Many plants give off scents to trick pollinators. One particular type of orchid has gone a step further and found out how to mimic the sex pheromones of some wasps. The poor wretches are tricked into thinking that the orchid is a potential sex mate and land on it to copulate. It's a SAD story really. Indeed, SAD - otherwise known as stearoly-acyl carrier protein desaturase - is the key enzyme in the synthesis of the fraudulent pheromone.
Protein(s): Acyl-[acyl-carrier-protein] desaturase 2
One thousand, every heartbeat. That is the rate at which sperm multiply in a healthy human male individual the moment puberty kicks off. It is a lot. And each sperm is potentially fertile. Ejaculation is therefore a very serious affair, and pushes one lonely egg into dangerous terrain if pregnancy is not desired. This is where contraceptives come in. Contraceptives for men - other than condoms and vasectomy - remain a tricky affair for a number of reasons. One being the sheer amount of sperm a contraceptive has to consider. Finding a solution at the level of the egg seems - naturally - less of a hassle than looking for something able to deal with millions of sperm at a time. Which is no doubt one of the reasons - though by far not the sole reason - that the popular pill came crashing into our society in the 1960s. Fifty years later, there is hope that a male contraceptive has been found. It all has to do with a protein known as Bromodomain testis-specific protein and a small inhibitor molecule known as JQ1.
Protein(s): Bromodomain testis-specific protein
Humans are unique. Whichever way you look at it. We can talk. We can write. We can build skyscrapers, make art, design weapons and be a general nuisance to many other life forms. About 2.5 million years ago however, our ancestors could not. So what happened? Something was needed to modify brain structure and spark off another form of intelligence. Genetic mutations are the answer to this. And natural selection of course. There is a gene, known as SRGAP2, which is found in the brain tissues of humans and our closest relatives - chimpanzees, gorillas and orang-utans. It so happens that SRGAP2 has a duplicate - SRGAP2C - which seems to be only found in humans. SRGAP2C is thought to have appeared at about the time the Homo genus emerged from the ancestral Australopithecus genus, about 2.5 million years ago. This would suggest that SRGAP2C had a pivotal role in forging the human brain, and was engaged in shifting our ancestors' somewhat rudimentary behaviour to more sophisticated ways.
Protein(s): SLIT-ROBO Rho GTPase-activating protein 2
Nothing is perfect. And nature is no exception. This said, we should be grateful for nature's imperfections because, were it not for them, we would not be here. Without the changes that have been accumulating in genes over millions of years, we would not know the rich diversity of species that inhabit Earth today. Yet we all know that mutations can be lethal to an individual. Tinker with a crucial position in a gene and you can find yourself with a severe handicap. Extensive damage to a cell's genome can lead to all sorts of ailments, not the least cancer. This is why Nature imagined DNA repair mechanisms so as to limit the damage and prevent as many mutations as possible. One such mechanism is nucleotide excision repair, and at its heart: protein Xeroderma Pigmentosum A (XPA).
Protein(s): DNA repair protein complementing XP-A cells
There is only one way of propagating the species, and that is by mating. However, for many animals, mating usually implies hordes of sperm all fighting to get their nucleus into one egg. The same goes for humans. It is perhaps an odd thing in the first place for Nature to have devised what seems to be an uneconomical procedure, and if an oocyte is fertilised by more than one spermatozoon, the ensuing zygote is not viable. So it was necessary to develop some modus operandi by which one sperm is allowed in, while the others are kept out. In fact, over time, animals have armed themselves with more than one strategy to avoid polyspermy. One of the most definitive is to act upon the zone which surrounds an oocyte - the zona pellucida - by making it impenetrable the moment one sperm has wriggled its way through it. Scientists have known for many years that this particular region changes its structure following fertilisation but they didn't know what caused the change. Until they discovered a protease, which has been dubbed ovastacin.
Protein(s): Astacin-like metalloendopeptidase, Astacin-like metalloendopeptidase
Pain is a persuasive way of keeping the enemy at bay. Hosts of living beings make use of it, both in the animal and the plant world. Many of us have experienced the sting of a nettle, or indeed a wasp, a cat's scratch and perhaps even the nip of a spider. And who hasn't used the end of their foot to assign a kick or two, right where it hurts? Besides spitting out a few venomous words... Not many of us, however, have actually come across a snake and the twang of its venom. As we all know - or have been told - a snake's bite can vary from being a little uncomfortable to excruciatingly painful and even harmful, not to mention fatal. Over the millennia, a snake's venom has been perfected and become a highly specialised cocktail of hundreds, even thousands, of molecules - most of which are proteins. Recently, scientists discovered a neurotoxin - dubbed MitTx - that causes pain via acid-sensing ion channels which run along the membranes of neurons. A novelty in the world of nociception.
Protein(s): Phospholipase A2 homolog Tx-beta, Neurotoxin MitTx-alpha
We all need sleep. Yet sleep spells 'off our guards' and, from a purely biological point of view, it is not a wise move. In the land of Nod, an organism is vulnerable and an easy prey for predator. So there must be something essential in taking a nap for Mother Nature to have thought it up. Indeed, when asleep, organisms are shut off from their surroundings for a period - a period they use to build up the energy they spend their time depleting when awake. It is all a question of vital energy balance. For such a system to work, however, we need something that not only measures our body's level of energy but also has a role in our sleeping behaviour. There happen to be many known systems that do one or the other but it is the first time that scientists have found a protein that reacts to levels of ATP and is directly involved in the length of time we sleep.
Protein(s): ATP-binding cassette sub-family C member 9
Pleasure is not a human invention. Experiences that arouse a feeling of contentment are as old as life. They have, in fact, kept life going. It is yet another of Mother Nature's tricks. If an organism perceives something as good, then it will do it again. If you want to keep a species going, the best way to do it is to reproduce. And, if the act of copulation is a pleasant experience, there's a fair chance you'll have another go at it. Eating, sex and social interactions are examples of acts most animals are accustomed to, and for which they are rewarded with a positive feeling. They also happen to be interactions which keep a species alive. But what happens when an animal meets frustration? Following rejection by a potential mate, for example? It finds some other way to quench its desires. Given the chance, Drosophila melanogaster will actually turn to alcohol if mating has been denied. Sex and alcohol are part of a highly complex reward system that has had plenty of time to evolve. Recently, scientists discovered the agent which orchestrates both behaviours: Neuropeptide F.
Protein(s): Neuropeptide F
We all take Spring for granted. The moment the first bouts of warmth hit the air, we fully expect to see the lawn duly mottled with daisies, leaves pushing their way into the nascent season and flowers blossoming wherever we care to look. And quite rightly so. We all know it's going to happen since it does every year. And we do realise that Nature needs to renew itself every once in a while. The process is - you could say - automatic. But it is only automatic because there are hordes of molecules that are able to recognise, in many different ways, the environmental cues - such as warmth and humidity for instance - and translate them into growth. An amazing state of affairs, if you give it a little thought. One such molecule, known as DELLA protein RGL2, has been the centre of attention amongst plant molecular biologists for some time now. Indeed, RGL2 is proving to be at the very heart of seed germination.
Protein(s): DELLA protein RGL2
Fingertips are hugely sensitive. And, besides the fairly recent mobile phones that rely on them entirely, we put their sensitivity to use constantly. They are able to grasp subtle differences in temperature and texture - such as discern warm from tepid for example, or a dry surface from a greasy one. They are also able to touch or feel extremely delicately. In truth, the ends of our fingers are able to give a pretty clear picture of what is happening around us. This, of course, is thanks to nerve ends which reach the very tips of them. But scientists are now suggesting that our digital refinement may also be partly due to the epidermal ridges which cover them. In other words: our fingerprints. Fingerprint architecture is slowly being uncovered, thanks to diseases that have the power to wipe them away. One such disease - known as adermatoglyphia - is caused by a deficiency in a protein known as SMARCAD1.
Protein(s): SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1
Someone once told me that they had spread grease all over the drainpipe that crawled up the front of their house, to prevent cats from climbing up it. It's a very simple and pretty harmless way of keeping the enemy away. It's hardly surprising, then, that Nature thought up just the same trick millions of years ago. Many higher plants' stems - and also sometimes their leaves - are covered with a whitish surface, which is slightly greasy to the touch. Botanists have known for a long time that wax in plants has many roles and that the powdery blooms on stems seem to be involved in keeping harmful insects away. The question is: how? But perhaps even just as important a question is: what makes the wax? Because if scientists are able to be on a more intimate level with what produces it, then they will be able to think up insect repellents that are more in keeping with Nature's ways. Not so long ago, researchers discovered an enzyme which synthesises lupeol, the wax component which forms the greater part of the powdery bloom.
Protein(s): Lupeole synthase
I would hate to leave the house without the odd necklace hanging round my neck. But I happen to be fortunate. Millions of other people are not. That is because a lot of jewellery contains the silvery-white metal known as nickel, which can cause disagreeable skin conditions. If nickel were confined to jewellery, things would not be so bad but it is also frequently found in zips, coins and mobile telephones for instance. And who, in our society, can easily dispense with any one of these items? 65 million people in Europe suffer from nickel allergy; that is a large part of the population. Nickel ions are able to creep off a necklace or a coin - following sweat or rubbing for example - and sink through the first layers of skin where they will trigger off an immune response resulting in dermatitis. But why does it happen in some people and not in others? The answer seems to reside in a very small region of a protein known as the toll-like receptor 4, or TLR4, which has been shown to be at the heart of nickel allergy.
Protein(s): Toll-like receptor 4
We are reminded regularly of how fragile life is and how easily the subtle balance of our molecular make-up can be shifted and cause devastating effects. Deafness is one. Deafness can be brought about by a number of incidents. It can occur following an illness or an accident for example. Or it can be congenital. Pendred Syndrome afflicts one out of two thousand human beings and is characterised not only by deafness in both ears but also - though not always - by a swelling in the thyroid gland, otherwise known as goitre. The symptoms of Pendred Syndrome have been known for over a century, but scientists are only just beginning to understand what it is that can leave a human-being deprived of a sense which is so vital. One of the culprits is known as Pendrin - a protein which acts as an ion transporter.
When I leave for work every morning, I know exactly where to get my train. This may sound quite absurd but just imagine, for one moment, that you had no memory. You would always be losing your keys. You would never remember where you had left your shoes. And you'd probably fall down the front doorstep daily because you had forgotten there was one. Thanks to our faculty for memorising things, life is far easier for us. We learn how to talk. We learn to avoid awkward situations. We even remember who our children are. On the molecular front, there is a lot going on. It all has to do with neurons and their ability to pass on messages and connect to one another. Unsurprisingly, many proteins are involved in the processes of learning and memory, and much research has been done on them in the past years. There is one protein, however, known as RGS14, which is a bit of a conundrum. Indeed, RGS14 seems to have the intriguing role of suppressing memory...
Protein(s): Regulator of G protein signaling 14 (RGS14)
Destruction is sometimes necessary for life to continue. It may sound paradoxical but examples are many. Our body shreds the food we eat to use the parts to feed itself. Certain cells commit suicide when they are of no use anymore. And damaged proteins within our cells are degraded and disposed of before they do any harm. Unsurprisingly, these are processes which involve multiple molecular interactions and are part of complex biochemical pathways - and when something goes wrong, our body is likely to feel the consequences. There is growing evidence that Parkinson's disease (PD) may well be caused by the accumulation, in certain neurons, of damaged proteins which - under normal circumstances - would have been degraded. Whether it is the accumulation of non-degraded proteins or the subsequent modified turnover of specific proteins which are the cause of PD, no one knows. But scientists have discovered one particular protein, suitably baptised "Parkin", which seems to be at the heart of the matter.
Protein(s): E3 ubiquitin-protein ligase parkin
Besides Dr Jekyll, humans cannot become something else after dinner. Bees can. Feed honeybee larvae some royal jelly, and they will grow into a larger, fertile and longer-lasting individual. It is no scoop. Scientists have known about it for over a century now. Nonetheless, it is a very thought-provoking notion for biologists - it means that a living being's fate can be quite dramatically altered depending on what it feeds upon, very early on in development. The systems we are most acquainted with have a strong genetic component; give us a gene, with an environment, and that will make you into a heavy-built, tall, bald or curly-haired person. But here is some jelly that will shape a bee's destiny. More specifically, there is a protein in the royal jelly that seems to be able to trigger off a series of metabolic processes in bee larvae, which will gradually turn them into queens. The protein has been baptized royalactin.
Protein(s): Major royal jelly protein 1 (Royalactin)
Talk about the other side of the coin. There is growing evidence that creativity may well go hand in hand with psychosis, in particular schizophrenia. Intuitively, it does not seem so far-fetched a notion. Just think of Salvador Dali, for example. Or Peter Sellers. But mental illness has been around for as long as humans, so why does evolution bother to preserve it? Precisely because of the advantages of a creative mind. Researchers are not suggesting that someone suffering from a mental disorder is inevitably a potential artist. Or vice versa. At least not quite... But what they are slowly demonstrating is that there seems to be a genetic predisposition for creativity and psychosis. And that this predisposition has exactly the same origin for both traits. More specifically, a protein known as neuregulin-1 may have the capacity - given the environment - to tip a mind into mental illness or genius.
It can take ages to meet the right partner. So much so that plants lost their patience millions of years ago and thought up something else: the art of selfing. Many flowering plants are indeed capable of extensive in-breeding - by way of a rather subtle form of hermaphroditism - to ensure their spread and survival. The common mouse-ear cress, Arabidopsis thaliana, which has become the model plant for botanists, is revealing how many plants are able to perpetuate their species by letting their pollen fertilise their own pistil. Which prompts the question: how does any given plant species avoid self-fertilisation in the first place? The answer, or at least part of it, is: the S locus. The S locus carries two genes whose protein products - SCR and SRK - are directly involved in A.thaliana's capacity to self-pollinate or not, and may well illustrate the pathway used by many other plants.
Protein(s): Defensin-like protein A, SCRA
There are a number of biological molecules which are involved in a bewildering amount of activities. Serotonin is one. First thought to have the sole potential of contracting blood vessels, over the years serotonin has demonstrated that there is more to it than meets its chemistry. Besides its vasoconstrictor properties, it is also believed to be involved in instances as diverse as embryonic development, mood, appetite, nausea, sleep, body temperature, ageing, premature ejaculation, pain, anxiety, aggression, memory, cognition and migraines. And no doubt, as time goes by - as it inevitably does - yet more activities will be added to serotonin's already impressive panoply. It is hardly surprising, then, that serotonin has been shown to play a part in psychiatric shortcomings such as obsessive compulsive disorder and impulsivity. But serotonin cannot do this by itself; it needs a receptor to which it can bind. A receptor known as the 5-HT receptor.
Protein(s): 5-hydroxytryptamine receptor 2B
We get on with our day-to-day life largely unaware of the continuous battles that are being led within us. Indeed, it is thanks to unceasing cellular hostilities inside our bodies that we are able to get on with our lives as we do. Unwelcome entities such as viruses, but also tumours, would use our bodies as a playground - spreading havoc in their wake - were it not for a system that Mother Nature has offered every multicellular being, namely an immune system. In particular, natural killer cells and cytotoxic T lymphocytes are able to recognise infected cells in the body, into which they inject various molecules that ultimately destroy them. But how is the death sentence relayed? By way of pores. And these pores are formed by proteins known as perforins which assemble into large aggregates to form a barrel-shaped tunnel through which the poison flows from one cell to another.
Imagine reading these words and not being able to pronounce them. Or reading them and not being able to grasp their meaning. These are just two of the drawbacks that many children - and adults - suffer from. In fact, we all know of someone who suffers from a reading disability, a common form of dyslexia. And that is because five to ten per cent of the population is afflicted by it. Because of its frequency, much progress has been made to try and understand why some children are simply not able to deal with words the way their classmates are, and yet they lack neither intelligence nor education. In the past years, it has become clear that dyslexia seems to have a hereditary component thus implying that a gene, or a collection of genes, could be at the heart of it. In the recent past, scientists have managed to track down at least one protein, with the appealing name of KIAA0319, which may well have a role in dyslexia and is involved in brain development.
Protein(s): Dyslexia-associated protein KIAA0319
Many of us are acquainted with headaches. Brought on by lack of sleep, a lot of alcohol, too many tears, the time of month, or even the time of year, clammy weather, overbearing noise - you name it - headaches are a pretty common ailment many of us put up with on a regular basis. What is more, there are many painkillers on the market which are able to wipe away the symptoms within a matter of minutes. Migraines, however, are another piece of cake. The same environmental factors may trigger off a migraine but the symptoms are far more severe, frequently causing those suffering from one to remain bedridden until the pain has gone. Needless to say, headaches like migraines have no doubt been mankind's lot since our appearance on this planet, but what is responsible for the rhythmic thump inside our heads? There are two theories. One says that it all has to do with blood circulation. The second says that it's because of our neurons. Recently, scientists discovered a protein, known as TRESK, that seems to be directly involved in causing migraines. TRESK takes part in neuronal communication, thereby supporting the second theory.
Protein(s): TWIK-related individual potassium channel, Potassium channel subfamily K member 18
You need two humans for romantic love. That sounds straightforward enough. But you also need chemistry, as in chemical processes. It is an uncomfortable thought in a society where freewill is all the rage. Yet any of our feelings need a basis on which to work upon. And that is our brain with all its neuronal circuits and neurotransmitters that are being continuously fired from one neuron to another, sending messages of fright, anguish, enthusiasm, sadness, despair, love and surprise to name but a few. So what would be the chemistry at the heart of romantic love? Serotonin. Perhaps... With a notion as ungraspable as love, it is a very tricky business to try and pin it down to the makings of one molecule. Yet that is what a team of scientists tried to do. Their research hypothesis is particularly intriguing: they compared the infatuation we all experience in the early stages of love with a form of obsessive-compulsive behaviour.
Protein(s): Sodium-dependent serotonin transporter
We give very little thought to the first breath we took as we entered this side of reality, and yet it was one of the most traumatic experiences we have ever been through. So much so, it is probably not such a bad thing that we have no - conscious - recollection of it. Each one of us spent the most part of nine months floating in amniotic fluid inside our mother, with oxygen being pumped into us via the umbilical cord. Once born, the umbilical cord is taken away from us and we have to find another way of providing our body with oxygen. Fast. That's when the tiny newborn - that we all were - starts using its airways which, up to that point, had been on standby. Something, however, has to boost them into action. Recently, researchers discovered the doings of a protein, known as 'teashirt homolog 3', which has shown that it most probably has a direct role in life's first breath - not in sparking it off but in preparing the grounds to welcome oxygen and deliver it to every part of our body.
Protein(s): Teashirt homolog 3
The smallest of things can have drastic consequences. A rash gesture. A reckless statement. A moment's hesitation. Likewise, the smallest of chemical changes can be the cause of serious afflictions such as cancer, Alzheimer's disease, cystic fibrosis or haemophilia. Noonan syndrome is one such affliction and affects a newborn in one to two thousand. Typically, a Noonan child has a wide space between its eyes, is web-necked and small in stature. Unfortunately, the condition is also associated with congenital heart disease, learning problems, impaired blood clotting as well as many other features whose range and severity vary hugely in patients. Everyday, a child is born with Noonan syndrome, and one of the culprits is the tiniest of modifications which occurs on a protein known as SHOC2.
Protein(s): Leucine-rich repeat protein SHOC-2
There is a huge cucumber growing in the middle of our lawn. I paid it a visit the other day, pushing aside the huge leaves, and in so doing got stung on the tips of my fingers. I knew the sting came from the small hairs protruding from the stem but, until very recently, I had never given them much thought. Not until I discovered the world of trichomes. Trichomes and I have been co-habiting for many years. They give out stings or release perfume. They feel like velvet. Or like an unshaven chin. They are on my poppies, on my geraniums, on the nettles, on the tomatoes, all over my son's cactus and on the cucumber plant's stems. In truth, most plants have trichomes. Trichomes look like hairs and protrude from a plant's leaf, stem or flower. Very little attention had been given to them by scientists when they were first observed, well over a century ago. However, trichomes have turned out to be precious minute entities on the surface of plants and we now know of a protein which has a direct role in trichome differentiation: trichome differentiation protein GL1.
Protein(s): Trichome differentiation protein GL1
Movement is essential to all organisms. Long before the advent of legs for instance, Nature had devised cilia to satisfy the essential need of mobility - both self-mobility and the capacity to create mobility. These tail-like protrusions, which appear on the surface of many eukaryotic cells and are known as motile cilia, are capable of propelling protozoans forward, for example, or of pushing an ovum along the fallopian tube towards the uterus. A second type of cilium also exists. These are the sensory cilia, such as those that belong to our taste buds for example, and which convey the sense of taste to our brain. However, since the beginning of this new century, scientists have discovered yet a third type of cilium. Indeed, there is growing evidence that some motile cilia can also be sensory. Or vice versa. By way of illustration, researchers have demonstrated that motile cilia located in the lungs can actually sense noxious substances, thanks to the existence of "taste" receptors on their surface, and then whip them away to clear the airways.
Protein(s): Taste receptor type 2
He hadn't been able to dial the full number for some time. But he had told his family that the phone was out of order. Until one of his daughters realised that it was not the phone which was faulty but her father's memory. This is just one of the many manifestations of what could be the beginnings of Alzheimer's disease (AD). A disease which affects millions of people worldwide, and sends their families into a whirlpool of doubt, impatience, pain and disbelief. Slowly but surely, Alzheimer's takes a hold of the patient's brain, causing damage to its neuronal structure and hampering its cognitive faculties. In time, the patient fails to recognise his or her own family besides suffering from disturbed basic vital functions, and the family members have to learn to deal with the loss of someone dear who is still alive... With a little over 100 years of research into AD, scientists are now able to diagnose the affliction relatively early. Despite this, there is still no medication which can cure a patient, though researchers have ventured down many alleys. One of these alleys involves a protein known as immunophilin FKBP52 which may have a future in stalling the progression of Alzheimer's.
Protein(s): Peptidyl-prolyl cis-trans isomeras FKBP4
When I was a child I remember seeing little girls and boys of my own age whose arms had not grown to their full length. There were not many but enough for me to find it almost normal. What I did not know is that there were other little boys and girls whose legs had not grown either. But we never saw them. As we never knew of all the little babies who died shortly after birth and whose limbs - and other parts of their bodies - were grossly malformed or simply absent. Such deformities were the doings of a drug known as thalidomide, and the children were known as thalidomide children. My mother refused to take thalidomide to treat her morning sickness when she was pregnant with her first child. Many other mothers, however, did not. And it was not long before the link between thalidomide and gross deformities found in newborns was made. How thalidomide created such handicaps remained a mystery for many years. Today, there are a number of hypotheses, one of which involves the protein cereblon which has turned out to be one of thalidomide's direct targets.
Protein(s): Protein cereblon
There is no life without communication. A heart will not beat, an eye will not see, a flower will not bloom, unless cells are exchanging information continuously. Such information comes both from the outside environment - such as light and temperature, for instance - and the inside environment - such as calcium, hormones or pressure, for example. Take a plant. A given leaf does not grow into its shape or size without the help of multiple upstream messages which have been processed, understood and performed accordingly. Thus giving the rose its petal, the cactus its needles and the fir tree its cone. A very intriguing question is how does a plant know when to tell a leaf to stop growing? In other words: how does a plant know when to tell cells to stop multiplying and expanding? Thus giving the leaf its final - and characteristic - form? The protein kinase ERECTA may provide an answer. ERECTA, or ER, seems to have a central role in relaying multiple messages to multiple pathways involved in plant development and architecture.
Protein(s): LRR receptor-like protein kinase ERECTA
The making of life is demanding. Take any form - from fungus to bacteria, and plants to humans - the creation of progeny does not just happen. It takes a lot of molecular dialogue to divide E.coli into two, to cloak pistils with pollen or to get sperm to wriggle its way into the egg. The most complex biochemical pathways are triggered off so that life can not only start to exist but also develop in the best way possible. Lately, some intriguing discoveries have been made regarding human sperm and how it finally makes it to the egg. The ongoing theory is that it may well sniff its way there. So do spermatozoa have noses? No. But they do have receptors on their surface, which are very like - if not identical - to olfactory receptors we have in our noses, and which can pick up scents. These odorant receptors are known as hOR 17-4. Could it be then that the egg exudes some kind of perfume to lure the sperm towards it? Perhaps.
Protein(s): Olfactory receptor 1D2
Words are not the only means of communication. Not only are they specific to the human species but there are many other ways of conveying messages, and - since the beginning of dawn - all kingdoms have shown great imagination in this area. Bacteria exchange information via chemical messages they secrete. Flowers produce scents to attract pollinators. Many animals are capable of turning on a possible partner by exuding pheromones. Releasing all sorts of molecules is one thing, but you also need something on the receiving end to sense them. These are receptors. There are many different kinds of receptors, found in many different tissues or cellular compartments, all of which are there to sense their matching molecule and relay the information further, i.e. the central nervous system in animals. Subsequently, the organism will be instructed to run away, let itself be seduced or avoid spoiled food, for instance. One particularly surprising receptor discovered in the nose of mice - a formyl peptide receptor - seems to have the ability to sniff out disease.
Protein(s): Formyl peptide receptor-related sequence 1, 3, 4, 6, 7
It is very likely that mint - and its close cousin menthol - is one of the most popular flavours or sensations known worldwide. Is there any population left on Earth that hasn't sucked a mint sweet or chewed on mint gum? Mint is drunk in beverages, and brushed onto teeth. Added to sauces, and put into chocolates. Smeared onto chests and added to paper handkerchiefs. Why is it that mint and menthol are found, one way or another, almost everywhere on this planet? Transport would be an obvious answer. But there is more to it than that. Besides the numerous health benefits, mint - and menthol - have a quality that is readily appreciated by many: freshness. This sensation is the legacy of two kindred proteins - P450 cytochromes - found in mint plants.
Protein(s): Cytochrome P450
When I was little, I used to wear little cotton shirts that were knitted by my grandmother. So? Well, onto them she sewed tiny nacre buttons you could never get hold of and which mesmerized me because of the different colours that shone off them depending on how you oriented them in the light. You can still find these buttons today but plastic ones have almost completely replaced them - and some even try to copy the lustre which is so particular to mother of pearl. What is it that makes pearl what it is known for? Aragonite. Aragonite is a calcium carbonate mineral and, very recently, scientists discovered a complex of three proteins in the pearl oyster Pinctada fucata, which seems to be at the heart of aragonite formation and orientation, and hence the famous sheen.
Protein(s): Pearlin, Pif80, Pif97
Charles Darwin has been resting in Westminster Abbey since April 1882 and scientists have been wondering ever since what it was that he suffered from for most of his adult life. It is a well-known fact that the famous naturalist steered clear of many official gatherings and was barely able to defend his theory of evolution because of chronic ailments of all sorts which kept him from being the sociable man he may otherwise have been. Many have thought that the origin of his various complaints - which were as diverse as vomiting, severe headaches, palpitations, eczema and flatulence - were purely psychosomatic. Others have suggested that Darwin must have been afflicted by some kind of illness such as Chagas' disease or, more recently, Crohn's disease. What everyone seems to agree upon though is that Darwin was definitely suffering from a form of gastrointestinal disorder which may well have involved an inherited lactose intolerance. Lactose intolerance is brought about by the lack of the enzyme lactase which breaks down lactose, thus making it digestible.
Protein(s): Lactase-phlorizin hydrolase
Making use of a tubular structure to inject something into something else is a widespread practice. Doctors use syringes to inject medicine into patients. Mammals use their reproductive organ to supply their female counterparts with semen. Wasps use their sting to insert venom into their enemy. And Encephalitozoon cuniculi uses a polar tube as a means to infect. E.cuniculi infects species throughout the animal kingdom. It does this by inserting a long tube into the host cell's membrane and injecting directly into the cytoplasm what it needs to proliferate. E.cuniculi is a parasitic unicellular eukaryote and thus cannot survive on its own. But the pathogen has to be able to recognise its host first. Scientists have discovered one protein - known as 'spore wall and anchoring disk complex protein EnP1' - which is found in the area from where the polar tube is thrust, and which is capable of binding to surface molecules on the host cell's membrane. Thus creating the cell to cell contact needed to trigger off infection.
Protein(s): Spore wall and anchoring disk complex protein EnP1
Life is sustained thanks to a continuous flow of chemistry within cells and between cells. Molecules of all shapes and sizes are being scooped up, modified, and released - albeit in a different form - to produce fuel, trigger off a metabolic process or indeed put an end to one, act as a messenger or simply become waste product. Until fairly recently, lactate was thought to be just that: a dead-end by-product following muscular effort for example. And for many a year, it was stashed away in the backs of minds as something which had no future. But it does. In the past decade or so, scientists have discovered that lactate has a life after all; it is not only being shuttled inside a cell but also from cell to cell, and may well have a role in telling our brain when a muscle is tired, or helping us to perceive muscular pain. As for most chemical entities, there are always proteins involved in binding to them, breaking them down or adding something onto them. One enzyme in particular is directly involved in lactate's career: lactate dehydrogenase, or LDH.
Protein(s): L-lactate dehydrogenase B, L-lactate dehydrogenase A
Drawing is probably not a talent the layman would normally associate with Science. Yet it has been an essential ingredient in the life of many scientists for the advancement of their field of research, among them, the Spanish neurobiologist Santiago Ramón y Cajal (1852-1934). Cajal contributed greatly to our understanding of the brain, not only in his writings but also by way of the fine drawings of his observations, which have always been heralded as a key element in conveying the evidence necessary to establish the neuron theory of the anatomy and physiology of the brain. Almost a century later, the world of brain research has gone one step further. Thanks to genetic recombination, scientists are getting proteins to draw for them. What is more, in colour and 3D... The artist's name is GFP - green fluorescent protein - a protein whose fluorescent properties have inspired many a researcher since its chance discovery in the 1960s.
Protein(s): Green fluorescent protein (GFP)
It's nice to have a warm place to mate. You may think this applies only to mammals. But it doesn't. Insects also love to breed in a cosy setting - in particular some beetles that have taken to coupling in large lilies which provide them with heat, as long as they stick around long enough to carry some pollen away. It's a clever invention, based on 'give and take' and a way-of-living largely put into practice by plants since they are stricken with immobility. They're ready to give insects a little of their nectar but they'll also make sure some of their pollen flies off with them for dissemination. How do lilies warm the place for beetles? By way of one of two respiratory pathways - known as the alternative one - which turns the energy produced into heat. A key enzyme involved in this alternative respiratory pathway has the sexy name of 'alternative oxidase'.
Protein(s): Alternative oxidase
The way to fertility can be a long one. When a bee innocently drops a grain of pollen in a flower, there is no guarantee that the ovary is close by. Mother Nature has not given pollen the means to walk but she has armed it with a built-in system - the pollen tube - which grows longer and longer until it reaches the ovary. The procedure is simple and effective, and in some respects not so different from our own reproductive system. Needless to say, such a structure needs to be both rigid and supple in order to preserve its shape while it elongates. How does it do this? At the end of the tube is a budding tip - the only part which grows. Here, a host of enzymes are hard at work either solidifying or softening the cell wall as the pollen tube germinates. Amongst these enzymes are the pectin methylesterases which are capable of turning the cell wall polysaccharide pectin into a rigid frame or soft jelly...
Protein(s): Pectinesterase 5
When Charles Darwin accepted the invitation to accompany Captain Fitzroy on HMS Beagle as the ship's naturalist, little did he know that he would bring back with him material that was to haunt him - one way or another - until the end of his days. Amongst the many mineral, plant and animal specimens which were unloaded from the ship on its return in October 1836, there were a number of preserved finches which Darwin had found on the Galapagos Islands. It was the study of these finches, which later became known as 'Darwin's finches', that helped to forge the notion of the transmutation of species. In other words, any given species had the capacity to adapt, evolve and undergo transformations - and it turned out to be in the name of survival. With regards to finches, their beaks were different depending on the kind of diet they had. Charles Darwin had no idea how such changes could occur within a species. Today, we are getting closer and closer to understanding how it happens on the molecular level. And it seems that a protein known as calmodulin has a major role.
Moving any one of our limbs is not something most of us have to think twice about. Rising from a chair to make a cup of coffee or picking your nose is usually a piece of cake. Yet the natural mobility of our legs - for instance - can be dependent on the existence or not of molecular loops. Nature can tease us with very little. Any one of our movements is made possible thanks not only to the existence of motor neurons but their growth and differentiation. Growth and differentiation are, in turn, dependent on many cellular activities, in particular the trafficking of entities from one end of a nerve cell to another. If the trafficking is checked for any given reason, the neuron does not react the way it should and whatever limb it activates will suffer the consequences. Spastin is an enzyme which has a central role in the building of highways for neuron traffic and we now know that it is also guilty of causing a neurodegenerative disease in the lower limbs, known as hereditary spastic paraplegia.
Every living being has devised a way to protect its embryos. Humans lodge them in wombs. Fungi protect them in spores. Butterflies keep them in cocoons. Nature's imagination has no limits. In order to keep life going, she has thought up hundreds - if not thousands - of ways of protecting her little ones. Some of her inventions are colourful indeed. Certain species of frog are capable of whipping up bright pink or orange foams in which are embedded their eggs, thereby hidden from predators or sheltered from challenging weather. A certain type of Malaysian tree frog, known as Polypedates leucomystax or the Java whipping frog, whisks up foam while it is mating, which gradually turns into a greenish blue on its surface. To what end? No one really knows. But we do know what it is that makes the foam blue: ranasmurfin.
Is there really a point to pain? Yes, argue most. Pain warns you that something is not right. It teaches children not to put their hands on a hot plate because they know heat hurts. It urges you to consult your doctor when pain persists in any part of your body. Yes, but what about pain that accompanies something which has already been diagnosed? What about the persistent pain that frequently escorts chronic conditions, such as a sore back or cancer? Who can see the good in that kind of pain? Though there may be instances when it seems superfluous and even cruel, the sensation of pain is more necessary than it is not. It is a clear indicator that there is something wrong, and that it needs to be seen to. In the absence of pain, no alert signals are given off - which could ultimately put your life in danger. It is a complex sensation with many a meaning and many a pathway. One particular pathway was discovered when members of a family were incapable of feeling pain - a singular and rare condition due to the loss of function of a protein known as SCN9A or Nav1.7.
Protein(s): Sodium channel protein type IX subunit alpha
Everyone knows what it feels like to lack sleep. The usual drive to get on with life is diminished. Problems are difficult to cope with. The urge to do any physical exercise is low. Short temper is just around the corner and the desire for a nap becomes greater as the hours tick by. Intuitively, everyone knows that you need to sleep to recharge the battery. It sounds simple enough because we know we feel restored after some rest and we've been living with it ever since we were born. But - like any physiological process - the act of sleeping is not so straightforward. Something inside us has to tell us: 'it's time to sleep'. And something else has to say: 'you need to sleep'. Our quality of sleep is driven by these two notions. Since the 1960s, scientists have been searching for genes which are at the heart of such processes. Recently, one protein named 'Sleepless' was discovered. Sleepless seems to be directly involved in telling us that all activity is to be put on hold for the space of a rest.
Despite their apparent slothfulness, some snails know how to put a predator on its knees. Intuitively, we are inclined to believe that defence involves not only speed but liveliness - two qualities which would not be those that spring to mind when describing a snail. So there is more to a snail than meets the eye. Indeed. Though the snails themselves may be the very image of idleness, they can produce molecules which can kill. Fast. This is nothing new. What is new, however, is that scientists have just found a toxin in a snail known as the apple snail, which is not only a protein but is also found in the snail's eggs. So, long before a snail has actually developed into a mature mollusc, it is outfitted with a means of defence.
We all take advantage of each other, one way or another. Cats hunt mice for food. Humans keep dogs for company. Flowers give off a scent to attract pollinators. Viruses use organisms to multiply. And ticks suck animal blood to stay alive. The tricks we use to these ends are varied and subtle. Flowers have put much effort into developing perfumes which are perceived by specific pollinators. Ticks have found ways of keeping blood fluid to be able to sip it. But it hasn't been easy. Adaptation has taken its time to fine-tune ways of making good use of another organism. Ticks, for instance, have thought up the finest of strategies not only to recognise an organism from which they can feed but also to land on it, fix itself to it and feed from it. Each step is crucial to a tick's survival. Understanding how a tick manages to shun its host's immune system - let alone keep its blood from coagulating - can be very informative for the development of therapeutic drugs.
There is no life without blood. Pumped through us by the heart, blood carries the oxygen we breathe and relays it to every part of our body to keep us going. If too much of it leaves us, life leaves us too. As a consequence, this rich red fluid has become a powerful social, religious and literary symbol. Our bodies also know how vital it is and produce red blood cells continuously to replace those that have gone past their use-by date. However, there are instances - an accident, an illness or surgery for example - when the amount of blood required exceeds the amount that a body can produce on its own. And the only way to solve the problem is by pouring fresh blood into the body which needs it. It sounds simple but it is not. Today we know that blood can only be transfused if both the donor's and the recipient's blood match. If they don't, our immune system will eventually kill us. Blood is always difficult to come by so years of research have been dedicated to finding ways of making it. Recently, a couple of bacterial enzymes were discovered, which could 'clean' red blood cells so that they could be transfused to any patient regardless of the blood group.
Protein(s): Alpha-N-acetylgalactosaminidase, Alpha-1,3-galactosidase A
Can a smell affect social behaviour? Without a doubt. Let off an unpleasant one and those closest to you will move somewhere else. Likewise, an agreeable scent will keep them hovering in your vicinity. It's an old trick. Flowers and animals have been using smells for millions of years to ward off predators or to attract individuals for the sake of reproduction. So it does not come as a surprise to learn that ants use the same kind of technique as a means of communication and social interaction. However, it is not so much the odour but the capacity to detect it that is at the basis of two types of social behaviour in a species of red fire ant, Solenopsis invicta - the ecological pest. This particular ant either belongs to a colony that has only one queen (monogyne) reigning over it or to a far larger colony which is ruled by several queens (polygyne). In the 1990s, scientists discovered that the basis of a monogyne or a polygyne colony amounted to the existence of only one protein: pheromone-binding protein.
Protein(s): Pheromone-binding protein Gp-9
What? No issue in July? A number of our regular readers may have noticed that – for the first time in a short decade – no article appeared during the month of July. And time has only just given us the opportunity to squeeze one into a month of August about to end. What happened? 2008 marks the 10th anniversary of the Institute. About a year ago, we pondered on the idea of conceiving an exhibition which would not only celebrate this little milestone but would also present the world of bioinformatics in as attractive a way as possible to non-scientists. It was not an easy task. For many, the word ‘bioinformatics’ is as sexy as the word ‘pots’, and the work carried out is as attractive as the bottom of a cake tin. Despite this and thanks to a year’s collaboration with scientists, writers and graphic designers – and the financial support of a few sponsors – our exhibition ‘Chromosome Walk, a saunter along the human genome’ is about to celebrate its opening, on September 1st in Geneva’s botanical gardens.
There are people who saunter through life unnoticed until something happens and reveals that they are far less ordinary than they appeared to be. The same goes for Heliobacter pylori. H. pylori is a bacterium which was discovered in the late 1800s but was forgotten for the best part of a century simply because no one had succeeded in cultivating it. Its role in causing gastric diseases was also discussed at the turn of the 19th century, only as the results were published in Polish they met with very little recognition outside Poland. And while H.pylori was being ignored, attempts were being made to study an enzyme which helps it to survive in the organisms it infects: urease. Like H.pylori, urease had to wade through waves of short-sightedness. Not only was it a common belief in those days that enzymes could not be proteins, but enzymes were also thought to exist in excessively low concentrations in plants and animals... Despite these barriers, H.pylori and urease finally triumphed at the end of the 20th century and both turned out to be singular entities.
We are surrounded by smells. Pleasant ones and not so pleasant ones, hard to distinguish ones, mild ones and strong ones. Smells are not part of our everyday life for the simple sake of pleasure. They are there for a purpose. The perfume of a flower can be used as an attractant for a potential pollinator, for instance. The scent given off by a poisonous mushroom is a way of warding off a predator and, by the same token, can be instantly recognised as toxic by an animal, thereby saving both species. Special scents are also given off by males and females when mating is in the air, and no wine grower will ever argue that a wine's fragrance is not for the sole purpose of seduction. But what is a smell? More often than not, a scent is made up of a mixture of odorant molecules which, together, will trigger off a complex olfactory system that will ultimately let us perceive it and, if we wish to, put words to it. The very first step in such a system involves an odorant receptor to which an odorant molecule binds. Recently, a new human odorant receptor - OR7D4 - was discovered. OR7D4 is special in that it is the first receptor known to respond to a specific odorant molecule.
Protein(s): Olfactory receptor 7D4
Triggering off the making of a baby may seem a pretty straightforward process. Which it is, from a certain point of view. Yet, before any decisive action is undertaken by a woman and a man in order to unite their gametes, sperm - like ovules - have already been through a very complex series of developmental transformations. Such transformations ensure that only sperm and ovules of the same species get involved with one another, for example, or that once a couple of gametes has united no one else is allowed in. Properties of this sort are expressed on the molecular level both on the sperm's and the ovule's surface. One such molecule is a receptor known as zp3 found in mammals. Zp3 is expressed on the ovule's surface and, though it is just one of many molecules, it is an essential one. Without it, sperm would not only be incapable of binding to the ovule's membrane but they would also most probably miss their target altogether.
Protein(s): Zona pellucida sperm-binding protein 3
Dogs were not meant to fit into a bag. Yet, some do. Consequently, instead of enjoying a healthy walk in the countryside they can go shopping with their owners. Convenience - both for humans and dogs - has trimmed down canine size in the past few hundred years. It is easier for dogs to be part of a household if they are medium-sized and more practical for humans to keep them if they are not too large. As such, natural selection coupled with selective breeding has supplied us with dogs ranging from barely twenty centimetres to giant samples which measure over one metre. And the stakes that a cross between a large poodle and a tiny Chihuahua will produce a medium-sized mongrel are high. So there must be a straightforward mechanism which is involved in their size. IGF1 - or insulin growth factor 1 - seems to be at the heart of such a mechanism. Indeed, scientists have discovered that small dogs all carry a certain variant of IGF1 while large dogs do not - or very few. This would suggest that the IGF1 variant has the power to reduce the size of a dog.
Protein(s): Insulin-like growth factor 1
When I was a little girl, I thought that my left-handed classmates were special. I envied their difference. And I used to marvel at the way they crouched over their desk, embracing something invisible as they did their best to avoid smudging ink all over their sheet of paper. Left-handedness is special. But so is right-handedness. Humans are not the only animals to make use of their hands - or claws, or paws, or hooves - but they are the only ones who show a marked preference for either the left one, or the right one. If this is so, there must be a reason for it. And not only must there be a reason but it must translate a certain structure of our brain: an asymmetry somewhere. Indeed, our brain is divided into two hemispheres which are dedicated to processing different activities. One side looks after our dreams, while the other is far more down to earth. LRRTM1 is the first protein to have been discovered which seems to be directly involved in this brain asymmetry. Consequently, it influences the handedness of a human-being and, more astonishingly, may also predispose individuals to psychotic troubles such as schizophrenia.
Protein(s): Leucine-rich repeat transmembrane neuronal protein 1
When there is nothing left to eat, we do not eat our parents or our children. We go down to the closest supermarket for food. Supermarkets, however, are not an option for bacteria. When they are short of nutrients, they are faced with a number of fates amongst which are sporulation, starvation or, for some, cannibalism. Indeed, Bacillus subtilis - a sporulating bacterium - has devised a way to feed on its sister cells in order to prolong its non-spore life. It does this by way of toxins which it produces itself and from which it must be protected to avoid committing suicide inadvertently... Needless to say, the molecular pathway is intricate and still obscure. However, hosts of proteins are being discovered, two of which are known as SkfA and SpdC whose actions result in B.subtilis sister cell lysis, from which the non-lysed cells will feed.
Protein(s): Sporulation killing factor skfA, Killing factor sdpC, Immunity protein sdpI
The end of December is a time of year when many lose their balance. This, however, is usually due to the numbing of the senses by an exaggerated consumption of alcohol. There are many other ways of losing your balance, and one of them can be caused by an altered architecture of the inner ear. Besides bearing the intricate machinery which allows animals to perceive sound, the inner ear is also responsible for our sense of movement. Those who are stricken with sea-sickness know all too well what this means. Very small regions known as the saccule and the utricle detect both gravity and acceleration, two forces we spend our time dealing with. Deprived of the capacity to perceive them, the simple act of moving our head would prove to be an awesome experience. At the heart of this perception are small stones. And one protein, otopetrin 1, is proving to be essential for their formation.
Life has its ways. We are given opportunities to make choices. We are even given opportunities to nudge life onto a path we wish. And yet, there seems to be an invisible force lurking beneath which leads you to the most unexpected places...an unexpected place which, in time, turns out to be the place where you should be. Call it destiny, perhaps. Today, fifty years after the day he was born, Amos is sitting in an office in Geneva at the head of a project which has travelled around the world and for which many people work. From a cramped attic to a large open space office, Swiss-Prot continues to grow both in work force and in use. Amos has won prizes for it. He has been praised for it. He has put much of his soul and his heart into it. And despite this, far from him was the desire of ever having really wanted it.
There is more to RNA than meets the eye. In the 1980s, students in biology were told that this molecule's raison d'être was to be a template for the making of a protein. RNA, like DNA, was made out of nucleotides and had no particular function other than that of being a text that was to be read. Today, almost 30 years later, there is growing evidence that little bits of single-stranded RNA are just as crafty as many transcription factors and can regulate the expression of a gene, and hence a protein. However, they cannot do it without the help of enzymes, two of which are known as Drosha and Dicer. Drosha and Dicer are ribonucleases which work in unison to sculpt RNA strands that in turn acquire the ability to bind to specific parts of mRNA, which they subsequently silence. As a result, the mRNA's product is not translated.
Protein(s): Drosha, Dicer
Autumn has come. So have the hunters. And stags have finished fashioning their antlers in their quest to seduce a partner, and fight off rivals. Besides copulation, antlers are one of nature's many wonders. Not only are they beautiful and sculptural but they are a rare example of an organ which regenerates, rapidly and on a yearly basis. Consequently, it is hardly surprising that scientists are spending a lot of time trying to unravel the underlying mechanisms which participate in the growth of an antler. Annexin 2 is just one of the proteins involved in antler regeneration, and more specifically in cartilage mineralization.
Protein(s): Annexin A2
When you're hungry, your thoughts go towards food. Without the urge to get up and find some, you're in trouble. It's a basic rule. Yet when transgressed one way or another, you can end up either overweight or underweight. It may sound silly because we feel - as humans - that we can decide for ourselves when to open the fridge or not. As it happens, we tend to an awful lot because eating is one of our pleasures. Consequently, we gather a surplus of energy which we stock around our buttocks and stomachs. However, given a little thought, moving for a meal is not so straightforward. Imagine a chicken whose organism needs fuel. If deprived of the sense of hunger, it may well do nothing about it, and starve. So there must be some underlying mechanism which pushes it to hunt down a grain or two; a mechanism which actually drives it to move elsewhere in pursuit of the calories it needs. Naturally, such a mechanism is always very complex. Yet scientists have discovered a protein - known as Bsx protein - which seems to be at the heart of both fidgeting and food intake, and hence of the propensity to be either stout or slim.
Protein(s): Bromodomain testis-specific protein
In 2002, Sylvie Déthiollaz and I were asked to imagine something that could entertain young children within the framework of a science fair. The fair was to be held in the Museum of the History of Science in Geneva, a neoclassical 19th century villa on the edge of Lake Geneva, which sits in the middle of a beautiful park. We had been thinking up activities for children for a couple of years already, which invariably involved coloured beads which we threaded onto a bit of wire to illustrate a protein's sequence of amino acids. We then folded the wire to give an idea of what a protein's 3D structure could resemble. The activity was always very popular, although frequently used as a spot where parents could leave their children while they wandered off to see something else. Besides our growing distaste in being used as a nursery, we couldn't face beads and wire anymore either and, quite naturally, we suggested writing up a tale for children instead. And "journey into a tiny world" was conceived.
Protein(s): Poietin, Pepsin, Albumin, Globin, Insulin, Actin, Myosin, Collagen, Immunoglobulin, Orexin, Crystalline
Dementia is a debilitating experience. For the afflicted, and for those who are close to them. Alzheimer's disease (AD) is a form of dementia from which millions of people suffer worldwide. Besides the well-known symptom of memory decline, people with Alzheimer's are progressively troubled by language impediments and peculiar visuospatial perception, for example, but also behavioural and psychiatric dysfunctions. Though the passing of the years is the main cause for what is known as sporadic AD, there is also a far more rare hereditary form. Rare or not, both types of AD are the result of irreversible neuron loss, brought on by protein deposits in the central nervous system. Detecting Alzheimer's is not a trivial affair. The first symptoms are not different from the normal process of aging. And it takes years before serious handicaps emerge. However, there seems to be one protein - known as apoE4 - whose presence is proving to be a sure indicator of whether or not someone is prone to AD.
Protein(s): Apolipoprotein E
We feel pain for a reason. Either to be informed of something that is likely to hurt us more unless we turn our backs on it, or of something that has gone wrong inside us. It is a sensation that has been evolving over millions of years, from yeast to man. Pain is multiple. Understanding its vocabulary and intricate syntax can shed light on what it is, why it is and how it could be countered. Detected by receptors, the sensation of pain can be kick-started from any part of our body. The TRP receptors are a family of such receptors, activated by an array of pain stimuli. They can detect hordes of different noxious chemical compounds but also environmental sensations such as extreme heat and cold. One particular TRP receptor - TRPA1 - comes as a surprise because, unlike many of the other TRP family members, it can detect multiple sensations leading to pain, as opposed to only one.
Protein(s): Transient receptor potential cation channel
Like us, bacteria have to move if they want to get somewhere. Or away from something. We take the bus, hop into a car, use our legs or climb onto a bicycle. Different bacteria have different means of locomotion that they have had ample time to perfect since their first appearance on earth millions of years ago. Some squirt slime to propel themselves forward. Or use flagella to swim in water. While others hitch a ride on a fellow cell, or project pili with which they heave themselves forward. Recently, researchers discovered yet another mechanism: gliding by way of minute anchors. Such motility systems always involve complex protein assemblies but one individual sticks out among the others: the adventurous gliding Z protein. AglZ is an essential part of the gliding mechanism some bacteria use to skim across solid surfaces.
Protein(s): Adventurous-gliding motility protein Z
Everyone knows how to tell the difference between a boy and a girl. The exterior signals are obvious. And yet, despite such a clear statement on Nature's behalf, the molecular pathways underlying our being either male or female are subtle and fragile. It takes very little to make a woman out of a man - at least as far as our chromosome makeup is involved. We were told that boys are XY, and girls XX. But it's not so simple. Some girls are XY, and some boys are XX... So there must be something sophisticated involved. And we are only beginning to discover what. Because of its singular architecture, the male Y chromosome is distinctive under the microscope and it was not long before 19th century scientists caught on that it had a major role in the making of a man. A closer look at it led molecular biologists to a specific region on the Y chromosome and, in the 1990s, scientists announced the discovery of a protein - the Sex-determining region Y protein (Sry) - that had a major role in convincing a foetus to become a baby boy.
Protein(s): Sex-determining region Y protein
Our grandmothers used to make jam in huge copper pans. The same copper pans that you would see hanging over the stove, with that distinctive green patina lining the inside. The same green patina that children instinctively knew was poisonous. And yet copper is essential to life. Without traces of this heavy metal in most living beings, a lot can go wrong because many enzymes depend on it to carry out their function. As a result, an organism must know how to keep copper at a healthy level - neither too high, nor too low. And this is achieved by way of transmembrane pumps which taxi copper in and out of cells. One such copper pump is known as the Menkes disease-associated protein because an American neurologist, John Menkes, first described an illness associated with this pump. Indeed, when the protein is deficient, it creates havoc.
Protein(s): Menkes disease-associated protein
When we raise a glass of wine, rarely do we give a thought to what has been involved in its making. Yet a wine's hue, its taste, its aroma, its sparkle and even the nature of its haze are given the same attention a mother would to her newborn. Many of the qualities of a wine are the doings not only of proteins inherent to the grapes, rice or any other product used to make it, but also to proteins which belong to yeast strains that are added for fermentation, and hence the production of alcohol. Consequently, it is hardly surprising that much time and effort is put into the identification and understanding of such proteins, in the quest to satisfy the palates and aesthetics of many. And the purses of others. Recently, two yeast proteins were discovered. The first is involved in the production of foam as the Japanese rice wine - sake - is brewed, and the second in the production of haze in white wine. Despite a difference in their functions, parts of their sequence are very similar, not to mention identical, and both belong to the cell wall of different strains of Saccharomyces cerevisiae.
Protein(s): Cell wall protein AWA1, Haze protective factor
Rarely do we give a thought to the minute world within us that keeps us going. Yet were it not for thousands of proteins, we would not be able to breathe. Or walk. Or smell. Hear, see or even think. How would we go to the shops? Drive a car? Take the bus? Write a letter? Read the newspaper? Or make a cup of tea? When things are fine, we feel invincible. It takes very little though to remind us how fragile we really are. The tiniest of entities can ground us. A virus can cripple us. Cells gone haywire can kill us. Chemicals can indispose us. A faulty gene can condemn us. And, more often than not, this molecular havoc is caused by proteins whose function has been diverted, modified or lost. Textbooks can explain it to us and even show some of it to us but the elegance of it is rarely grasped, at least by the layman. That is why art - in all its forms - can be a unique way of shifting the tiny into the world of the big. Mara Haseltine, an American artist and sculptor, has done just that by shaping a handful of proteins, to show both their beauty but also perhaps their ugliness on a human scale.
Protein(s): BLyS, Rhodopsin, Follicle-stimulating hormone alpha chain, Replicase polyprotein 1ab
There is no life without energy. Much in the way a car needs petrol to run, we also need something essential to keep us going. And it is called adenosine tri-phosphate or ATP. ATP runs through every nook and cranny of our body to keep our heart pumping, our fingers moving and our thoughts alive. But - like petrol - we do not get it for free. We have to make it. So, in the great majority of our cells, we have powerhouses - known as mitochondria - that spend their time synthesizing ATP and distributing it where need be. Not surprisingly, hordes of proteins are involved in this process, one of which has been known for decades: cytochrome c. Human cytochrome c happens to be the very first protein sequence that was entered into the Swiss-Prot database. And the beginning of an adventure which is heading into its 21st year.
Protein(s): Cytochrome C
All organisms need other organisms to survive. Flowers need bees. Frogs need flies. Humans need vegetables. And viruses need us. Poliovirus in particular squats human cells preferentially, where it uses their machinery to replicate and multiply since it cannot do it on its own. In doing so, poliovirus - like all viruses - hinders not only the host cell's welfare but also any activity it should have undertaken. However, before a virus stands a chance of invading a cell, let alone propagating inside it, something has to let it in. For poliovirus that something is a protein receptor, known as the poliovirus receptor. These receptors are sprinkled on the surface of certain types of cells and are specifically recognised by poliovirus, which docks to them and subsequently finds a way to wriggle inside.
Protein(s): Poliovirus receptor
The colour of human skin has been - and still frequently is - at the heart of violent controversy. Political, social and physical. Yet, as the science of human genetics unfolds, we are reminded over and over again that any given human population cannot be defined according to its pigmentation since any skin hue blends gradually into another. However, there is no doubt that there are dark skins, and there are light ones. The darkness - as the lightness - of skin depends on the amount of melanin present in the epidermal cells. And the amount of melanin depends directly - though not solely - on the existence of a protein that has been christened 'solute carrier family 24 member 5' or 'SLC24A5'.
Protein(s): Golden protein, Solute carrier family 24 member 5
We take our three dimensional architecture for granted. Yet, were it not for biological scaffoldings of different kinds, all living entities would probably be quite flat. Besides acting as something from which muscles and internal organs can hang, skeletons bestow on humans a characteristic shape. As they do on giraffes. On a far smaller scale, any specific cell also has a distinctive contour, given to it by what is known as the cytoskeleton. The cytoskeleton is made up - for the most part - of actin filaments, which are themselves assemblies of thousands of globular actin monomers. Cytoskeletons - like any scaffolding - need builders to be erected, and the protein twinfilin is one such builder. Twinfilin is intimately involved in actin filament dynamics, and without it there is not much that living entities could do.
Getting tangled into knots is rarely a desirable situation. Yet there is a protein whose entanglement is not only profitable but also so final that it can kill off bacteria that interfere with its host's feeding or living space. Microcin J25 is a small antibacterial peptide synthesized by certain strains of Escherichia coli during times of hardship. Its knotted structure is such that it interferes with the victim's RNA polymerases hindering RNA polymerization and hence protein synthesis. As a consequence, the targeted bacteria die off leaving refreshment and room for their rivals.
Protein(s): Microcin J25
Hearts beat, throats swallow and Fallopian tubes squeeze. Many parts of us are pumping, pushing, and expanding at regular intervals all day long. And the regularity of these intervals depends on intricate molecular pathways that we are only beginning to understand. Part of the secret is being unveiled thanks to a minute nematode - Caenorhabditis elegans - whose rhythmic movements are easy to follow simply because of its transparency. A protein similar to proteins already discovered in humans, and known as Vav-1, seems to be at the heart of rhythms in the worm, which allow it not only to swallow but also to conceive and - less romantically - to expel waste.
The world population increases daily, and with it the number of mouths to feed. As a consequence, finding ways to improve crop yield has become a major issue. Since the 1960s, grain production has grown exponentially. And while it took 10 000 years to produce the first billion tons of grain, it has only taken 40 years to produce the second, thanks to fertilisers, pesticides and intensive cross-breeding. As is frequently the case, the molecular mechanisms underlying the commercially improved phenotype are largely unknown. However, it appears that hormones known as gibberellins - along with the proteins they stimulate - have a central role in plant growth and development, and could be the molecules upon which to act in the future, to design cereals - or indeed other plants - that are favourable in terms of agronomy and economy.
Protein(s): DELLA protein Rht-1, DELLA protein dwarf-8, DELLA protein Gai1
Injury to the adult central nervous system (CNS) and neurodegenerative diseases often engender lifelong consequences to the organism. Could the key to the mysteries of nerve regeneration lie concealed in the amino terminus of a notorious protein? Independent research groups working on either side of the Atlantic have answered in the affirmative. Indeed, the legendary inability of neurons to regenerate and repair lesions in the adult CNS can be attributed to a battery of inhibitory and repellent proteins, one of which - dubbed Nogo - is released by nerve fibres following injury.
Protein(s): Nogo protein, Nogo-66 receptor
Trees are beginning to blossom, flowers are easing their way through the earth and frogs will soon begin their slow march out of hibernation. In short, Spring is on its way. And for the faultless unfolding of these awakenings, hosts of proteins will be summoned. Tau protein is one. Tau has become very popular since it was discovered that its presence seemed to coincide with the evolution of Alzheimer's disease. Though it may sound contradictory, tau protein could have a protective role towards neurons, as suggested by the process of hibernation in the European ground squirrel...
Protein(s): Microtubule-associated protein tau
The month of February is usually dedicated to romanticism. We, however, shall dedicate it to the intricacies of earwax. Less charming, perhaps, but just as colourful. Many of us are acquainted with the yellowish/brownish soft substance which lines our inner ear. Regarded mainly as dirt, we spend our time extracting it. Yet there is good reason for it to be there. And one of the reasons is due to the existence of cerumen apocrine glands in the external auditory canal, which secrete cerumen along with a host of other biomolecules. Secretion demands canals and pumps. And one protein pump - the multiple drug resistance protein 8 (MRP8) - has a direct role not only in the production of earwax but also its texture.
Protein(s): ATP-binding cassette transporter subfamily C member 11
The sensation of hunger would seem trivial to most, and yet - besides being vital - it implies complex molecular pathways both in our guts and our brain, as too does the perception of food sufficiency. Most of the time we are unaware, but we own a built-in system which tells us when our bodies could do with a little fuel, and when they can do without. An empty stomach - like a full one - does not go unnoticed. What is it that makes us feel hungry? Or full? Research on gut sensations has been blooming for years now, what with obesity spreading worldwide, and the molecular processes underlying appetite, or satiety, are slowly emerging. Ghrelin and obestatin are just two proteins which are an integral part of such processes, and are particular in that not only are they coded by the same gene but they have opposing actions. Indeed, ghrelin triggers off the desire for food, while obestatin reports adequacy.
Protein(s): Appetite regulating hormones ghrelin and obestatin
Christmas seems to come around faster each year. And with it, the inevitable sensation that time is truly passing and - though we may be getting a little wiser - we are getting none the younger. Like it or not, we are stuck with life the way we are stuck with the prospect of death. We can trick the traces of the passage of time with plastic surgery but underneath, our bodies are ageing without mercy. How? And is it genetic? Environmental? Both? Neither? A child's development into a full-grown adult bears a strong genetic component. It is not yet clear, though, whether the process of 'just getting old' does too - although a number of disorders which bring on premature ageing would suggest something of the like. A protein named Klotho, discovered by chance in the late 1990s, is helping to unveil the process involved in an individual's longevity.
The human brain has been a hot issue for centuries. Physical anthropology flourished in the 19th century and with it the science of craniometry compounded by a growing belief in biological determinism. Intelligence - that intangible quality - was quantified and said to be dependent on brain size. Criminality was based on facial features and cranial particularities. And the notion of racism became a bodily measurement. Thankfully, the 20th century offered the necessary wherewithal to tone down all these beliefs thanks to an ever-growing knowledge of the molecular processes going on inside the human body. Intelligence is no longer quantifiable and cannot be defined according to the size of a human brain. Criminality has nothing to do with someone's looks and population genetics have demonstrated that the notion of race has no real meaning. Despite all this, it is clear that modern humans would not be where they are, were it not for the size of their brain, and its grey matter. And we now know of a number of proteins that are involved in such a process, one of which is a protein known as microcephalin.
One of the beauties of Autumn is the firework of orange, yellow and red hues it displays. Anthocyanin is a plant pigment involved in this colourful palette. And not only in the autumnal shades but also in the reds, blues and purples of petals and fruit all year round. The array of colours offered to us by Nature has always fascinated scientists who have put a great deal of effort into understanding both the structure of the various pigments but also the pathways leading to their synthesis. The final steps leading to anthocyanin are performed by an enzyme known as anthocyanidin glucosyltransferase. And in roses, this particular enzyme catalyses not one reaction - as is the case in the production of other flower anthocyanins known to date - but two reactions which lead to rose anthocyanin.
Protein(s): Anthocyanidin 5,3-O-glucosyltransferase
We are all looking for attention. One way or another. Even spermatozoa. In its race to fertilise, a spermatozoon modifies the egg's surface thereby demolishing the hope of millions of its kind. It may lack fair play but it certainly is an effective way of grabbing attention. This is exclusiveness on the level of sperm. However, scientists are beginning to realise that semen also has its ways: coagulation. What better way to hinder the advancement of a supplementary troop of sperm than by the erection of a biological fortification? When semen is ejaculated, it coagulates almost instantly to then liquefy slowly, unshackling spermatozoa in the process. A number of chemical entities are involved, one of which is semenogelin, the protein which forms the coagulate scaffold.
Protein(s): Semenogelin-1, Semenogelin-2
Do we, or do we not, have a sixth sense? Yes say most. And it certainly does seem to be the case. Like many animals, we are capable of responding to sensory chemicals of which we are quite unaware - pheromones - and that can modify our behavior. We are, however, in the process of losing - though not all agree - the organ which may well have been used by our ancestors to perceive such an obscure sense: the vomeronasal organ which can be observed just in the inside of our nostrils. The intriguing part is that a subfamily of protein receptors, which suspiciously resemble known mammalian pheromone receptors, has been discovered in humans: the type 1 vomeronasal receptors. Could it be then that not only do we have a sixth sense but we also have an organ dedicated to it? Just like in the good old days?
Protein(s): Type 1 vomeronasal receptor
Any scent conveys a message. It can be a nice one or not such a nice one but a smell always has something to say. And living organisms of all forms and sizes make great use of scents in matters so crucial as reproduction or more down to earth as mere survival. A scent can ward off a predator or, on the contrary, attract an admirer. Flowers are great users of smells; since they cannot move around the way animals do, they make sure their scented emissions can. And they know when to let a whiff off. A scent is a combination of chemicals that a flower synthesizes. A flower, however, will not release a fragrance unless it needs to. What is it that orchestrates the biosynthesis and subsequent emission of a smell or not? In petunias, a protein known as ODORANT-1 seems to be at the heart of smell: without it, a petunia's petal would be scentless.
Protein(s): ODORANT1 protein
Life is not static. Despite the apparent coolness of living matter's external features - save for the twitch of an insect's antenna or the flick of a chameleon's tongue - our insides are seething. Molecules of all shapes and sizes are being frantically - and continuously - ferried from one part of our body to another by way of an intricate mesh of highways and side roads which bear as many sign posts and traffic regulations as any regular metropolis. When humans need to go from A to B, they climb into a car, hop onto a bus or thumb a ride. What kind of transport do proteins use? Or other biomolecules? Well, there seem to be as many means of 'biotransport' as there are makes of car. And one is the Lipid Transfer Particle (LTP), a lipid shuttle found in insects, the scaffolding of which depends on a particular type of protein: the lipophorins.
Tintin never grew up. Readers followed his travels around the world for almost fifty years and yet the Belgian journalist showed no signs of aging whatsoever. No grey hair, no wrinkles, no loss of stamina. He never changed style either; he never seemed to tire of his knickerbockers nor of his cranial crest. But that is beside the point... How can a human span a lifetime looking as though he never grew older than the age of fifteen? Hypogonadotropic hypogonadism or HH say some. HH is a condition in which the subject who is inflicted with it never reaches puberty. Typically, in a man, this would mean that he shows no signs of becoming one, i.e. in growing facial hair for example or being the proud owner of a mature reproductive system. Tintin never took his pants down but any of his readers know that he certainly never showed signs of growing a beard. HH in a man is caused when the regulation of the male hormone, testosterone, is deficient. And we now know of one protein which seems to have a key role in such a regulation: the KiSS-1 receptor.
Protein(s): KiSS-1 receptor, Metastasis-suppressor KiSS-1
There is not much we have in common with sweet corn and yet, when you take a closer look at the way an egg cell is fertilised in flowering plants, it is difficult to avoid making comparisons with humans. A long tube - the pollen tube - must make its way into the female gametophyte and release its sperm cells which will then fertilise the egg cell. The great difference however is that a pollen tube has to elongate and travel quite far to perform its business because pollen - unlike sperm - is not mobile. A number of questions arise. What, for instance, guides the pollen tube towards the gametophyte? And how does it know when it has reached it? Scientists have found the beginning of an answer in the form of a small protein: Zea mays EGG APPARATUS 1 or ZmEA1, which has a role in pollen tube guidance and orientation in the phases preceding egg cell fertilisation.
Protein(s): Egg apparatus-1 protein
After a century's ban, Switzerland has legalised the production of absinthe - the emerald-green liquor which was said to have caused the madness of many throughout the 1900s, one of whom was the Dutch artist Vincent van Gogh. The beverage is prepared by macerating a cornucopia of spices and herbs such as aniseed, fennel, hyssop, lemon balm, angelica, star anise, dittany, juniper, nutmeg, veronica and wormwood oil in alcohol. It is hardly surprising that, upon abuse and on a long-term basis, such a mixture of chemicals should have an undesirable effect on our system. Nevertheless, at the dawn of the 21st century, a greater understanding of absinthe's claimed toxicity is surfacing and fingers are pointing at thujone, a terpenoid found in wormwood oil. Besides lending absinthe its particular flavour, thujone has the ability to bind to receptors in our brain - gamma-aminobutyric acid A receptors or GABAA receptors - which can bring on a number of brain disorders.
Protein(s): Gamma-aminobutyric-acid receptor
To what end do we need to taste? Just to enjoy a night out at the restaurant? Fish can also taste. But they do not go out for dinner. We - like all animals - taste because we have to be able to distinguish between what is good for us, and what is not. Nowadays, things are easy. All you have to do is saunter down the road to the nearest supermarket and pick out what you need. Most of us can read, and relate the word 'tomato', 'steak' or 'chocolate' to a taste. Thousands of years ago, though, there were no supermarkets (or chocolate) and our ancestors could only rely on their taste buds. As a consequence, they learned that sweet-tasting foods were probably edible, whilst bitter ones were probably not, because - more often than not - bitterness spelled poison. And the distinction we are able to make between sweet and bitter resides in taste receptors which are lodged in the recesses of our taste buds.
Protein(s): Sweet taste receptor
In the early days of the last century, scientists believed that the colour of our eyes was a straightforward inherited trait. Mendel's laws of inheritance had become fashionable and eugenicists saw in them an elegant and practical way to define our species. However, as the years passed and research in genetics progressed, ascribing the pigmentation of our eyes to the powers of a sole gene soon showed its weaknesses. Pigmentation proved to be a complex biological process. Nevertheless, as the 20th century bows out and the 21st bows in, it appears that - though pigmentation as a whole is part of an intricate biochemical network - the colour of our eyes does indeed seem to be in the hands of one gene which codes for a protein known as the P protein.
Protein(s): P protein
Proteins have made it into the world of Art! In 2002, Julian Voss-Andreae - a physicist cum artist -used a Protein Spotlight article as a source of inspiration for one of his sculptures. The protein he chose to sculpt was Kalata B1, a polypeptide with a very special twist in its sequence which forms what is known as the Moebius strip. Kalata was not the first protein Julian undertook to portray, nor would it be the last. Green fluorescent protein (GFP), mating pheromone ER-1, light-harvesting complex and a viral capsomer have also been moulded by the artist's hands, not to mention a homage paid to the man who discovered the alpha helix structure by erecting a huge replica in front of the scientist's boyhood home - now known as the Linus Pauling Center for Science, Peace and Health.
Protein(s): Green fluorescent protein, Kalata B1
Could chemistry be at the heart of sexual wanderings? Or of sexual devotion? Though the idea certainly lacks romantic appeal, there are signs which point in this direction. The neuropeptide vasopressin is not a newcomer to research on animal social behaviour. However, narrowing one of its roles down to what scientists coolly term 'social cohesion', and Christians call 'infidelity', is a breakthrough, and deserves some thought. It is not so much the quantity of vasopressin but the tissue distribution of its receptor - in males - which seems to have a role in defining flirt or faithfulness.
Protein(s): Vasopressin V1a receptor
Humans can talk. Other animals cannot. So there must be something inside us that is quite particular to the species. Certainly, the human larynx is placed in such a way that it supports our vocal miracles. But the positioning of the larynx itself is not at the heart of our capacity to form words, nor to learn them, remember them, reproduce them and place them in an order which makes sense to our listeners. All this demands neuronal as well as motor facilities, which are unique to humans. Could the art of speech be genetic? 'Well...kind of', say researchers. There certainly seems to be growing evidence that the human faculty of vocal communication bears a genetic component. And who says gene, says protein... FOXP2, a transcription factor, was discovered a few years ago and, though its exact function remains unknown, it is now quite certain that it participates in human language skills.
Protein(s): Forkhead box protein P2
Who would have thought that a virus could have anything to do with a tissue as important to life, and its development, as the placenta? A viral protein, now known as syncytin, whose gene was probably integrated into the primate genome over 25 millions years ago, is hugely expressed in placental tissue - especially at the beginning of embryonic development - and is giving signs of bearing an essential role in placental architecture. Could it be that placental evolution - and indeed mammalian evolution - finds its origins in the doings of a virus?
One higher primate gained recognition for being sent up into space, another for memorising language signs and yet another for saving the life of a young boy. But none of them reached the heights of fame the albino gorilla 'Snowflake' reached: Snowflake was the first case of albinism in great apes ever recorded. He suffered from the well-documented pathology: oculocutaneous albinism type 1 (or OCA1). This type of albinism is the most common form in humans and is caused by the malfunction of a tyrosinase, an enzyme which has a key role in the synthesis of the pigment melanin.
Beer has been around for thousands of years. Beer foam has not. Beer foam, as indeed beer haze, is one of today's hot topics in the world of beer brewing. Besides a beer's taste of course. What a beer should look like - once served in a glass - has become paramount for a brand's commercialization. And that is why there has been much bustle around the chemistry at work in such a process. It has been known for a while now that a number of proteins, or more correctly polypeptides, are involved in foam formation but it wasn't possible to pinpoint which protein was more involved than another. Finally, it appears that one barley protein has managed to wriggle out of the crowd. And what might that protein be? Lipid Transfer Protein 1 or LTP1.
Protein(s): Lipid Transfer Protein
When referring to prions, most of us think 'Mad Cow disease' (Bovine Spongiform Encephalopathy or BSE). Which is not incorrect but narrow-minded. The term 'prion' - coined in the early 1980s by the American biochemist Stanley Prusiner - simply means 'infectious protein', from which were derived the letters which make up the word. Prion proteins are found not only in cattle, sheep and humans, but also in other vertebrates as well as yeast and certain fungi. And will no doubt continue to be discovered in many other organisms, if not all. The URE2 protein - a candidate prion in Saccharomyces cerevisiae - was the first prion to be crystallised. Clearly, the understanding of a prion's 3D structure and the conformational changes it undergoes - and passes onto its peers - is of great interest in the search for therapeutic treatments of diseases caused by these volatile proteins.
Protein(s): URE2 protein
'What's a fossil Mum?' To which most Mums would answer, 'A fossil, sweetie, is bone which has become stone because it's been lying somewhere for a very long time.' The process of bone diagenesis is a complicated one but on the whole Mum's answer is not incorrect. However, before the bone becomes absolute stone and depending on the environment, some organic parts can survive for a long time. Even millions of years. And these are excellent candidates for study. Scientists have already managed to extract DNA from fossil bone - though in poor condition. Which is a pity, because DNA - though minute - can stash huge amounts of information. What is needed is something that not only lasts but is also informative from a biological point of view. A protein perhaps?
Face-to-face combat also exists at the molecular level. With time, animals have developed the means to fight off foreign bodies by way of a complex immune system. But it can be countered. Recently, it was discovered that the defensive effects of one protein (APOBEC3G) - found mainly in human T lymphocytes - could be wiped out by the actions of a second viral protein (VIF) which neutralises it. The net result is viral infection of human T lymphocytes. VIF belongs to Type 1 Human Immunodeficiency Virus (HIV-1) and seems to be crucial for the development of viral infection; whilst APOBEC3G, without the counter-effects of VIF, can ward off HIV-1 infection on its own. The great interest is that novel therapies developed around APOBEC3G and VIF should be of tremendous help in the endless struggle to design drugs which could fight off HIV-1 infection effectively.
It is hardly the time to talk of mosquitoes when the cold winter winds are still blowing. In milder climates though, mosquitoes are out and about, causing millions of deaths every year through their ability to transmit diseases, such as encephalitis, dengue, yellow fever and, of course, malaria. According to the World Health Organization, malaria alone is the cause of over two million deaths in Africa, one million of which are children under the age of five. The mosquitoes that transmit the disease belong to more than one species and they are collectively known as the anopheline mosquitoes.
Protein(s): Odorant receptor Or1
Ever heard of diatoms? Diatoms are phytoplanktonic unicellular algae that populate soil and seas around the globe. They are so small that many are indistinguishable under the light microscope - with dimensions ranging from a few micrometers to only a millimetre. Yet despite their microscopic size, diatoms are one of our primary sources of oxygen. Which just goes to show that minute can also spell merit. There has been a growing interest in diatoms - or their exoskeleton - in the past decade because they display the most intricate bioarchitecture ever seen...and in glass, if you please. The glass shells that surround the microalgae are nourishing the imagination of nanotechnologists. And diatomists are just beginning to decipher the molecular mechanisms underlying diatom shell masonry. One of the masons is called silaffin. Silaffins were discovered in the diatom Cylindrotheca fusiformis; they are an intimate part of the diatom glass matrix and are endowed with architectural talents.
Protein(s): Silaffin 1
Bubbles are not reserved to the likes of champagne or beer. Our cells also sprout bubbles - or vesicles. Vesicles are formed by means of two cellular processes: exocytosis and endocytosis. The point of such bubbles in living organisms is to relieve the plasma membrane of a number of constituents. Be it to down regulate a pathway - by removing a given receptor from the plasma membrane for example - or to transport molecules from one side of a cell to another. One species of vesicle - the clathrin-coated vesicles - are particularly important in vesicle trafficking in endocytosis and in exocytosis. And in the process of endocytosis, one protein - epsin - has a major role in the initial steps of membrane budding.
This is not an article on what multiplies your cholesterol level over the Christmas period. Or on what brings on - for some - terrible bouts of depression as the festivities draw in on them. But it does have to do with December 25th...in a way. The 'Christmas factor' is a protein whose deficiency was first discovered in the 1950s in a little boy by the name of Stephen Christmas. Also known as factor IX, or FIX, it is involved in blood clotting and its deficiency causes the rare form of congenital male hemophilia: hemophilia B. And coincidences being what they are, the article announcing the discovery of the Christmas factor was actually published in the 1952 Christmas edition of the British Medical Journal!
Protein(s): Christmas factor
A prolonged and healthy life is a tempting prospect. Especially in a day and age where there seems so little time to fulfil our ever-growing aspirations. Researchers have been giving a lot of their time to the problem of longevity since the 1930s, when it was first discovered that calorie restriction actually lengthened life expectation in mammals. It took many more years before scientists caught a glimpse of the molecular pathway underlying such a process. And, for the time being, it really is just a glimpse - but an encouraging one. A family of proteins, known as sirtuins (sir-too-ins) or SIRS - an abbreviation of Silent Information Regulators - and which are found all the way from bacteria to humans, seem to have a role in the ageing of cells, and hence the ageing of organisms.
Protein(s): NAD-dependent histone deacetylase SIR2
For some, garlic just spells bad breath. Yet it is a vegetable whose past is far richer than its smell. Botanists believe that it was one of the first plants to have been domesticated; ancient remains have been found in habitats which date back 10'000 years. The plant probably originated in Asia and made its way slowly to the West, leaving in its wake the most diverse folklore and beliefs. The Hindus, the Scandinavians, the Greeks and the Germans believed that garlic had protective powers against evil influences. In Norse mythology, garlic was worn to ward off trolls. In central European mythology, it fought off witches and vampires, so much so that a man who refused to eat garlic was considered to be a potential vampire! Garlic cloves were thought to impart strength and bravery and as a consequence were fed to the Egyptian pyramid builders and Roman soldiers. And all because of a pungent odour...
Protein(s): Alliin lyase
Most of us take the oxygen we breathe for granted. Yet were it not for the plant kingdom, and a large and slothful enzyme, none of us would be here. Rubisco is the key enzyme which - in the process of photosynthesis - swallows up atmospheric carbon dioxide and deals with it in such a way that oxygen is released into the air. The release of oxygen is really just a side effect. Rubisco has no particular feelings for humans; it just uses the carbon from the carbon dioxide, which it recycles as sugars for its own selfish purposes. In the same way that we breathe in oxygen for life's sake and recycle the waste as CO2.
We have all stuck our fingers down a drain and felt that viscous slime that lines its walls. Revolting though it may seem to our tactile senses, such biofilms - as they are known - are a world in themselves. The slime is secreted by various microscopic organisms and - despite a poor understanding of its function - it is used in a number of industries, including the food industry, for its viscous properties. And today, scientists are discovering the potential of this gelatinous matter in the field of therapeutics. What is this slime made of? Mainly, the polysaccharide alginate. And GDP-mannose dehydrogenase is the enzyme which has a major role in its biosynthesis.
Protein(s): GDP-mannose 6-dehydrogenase
Though we appear to be quite solid, we are in fact quite liquid. Like all living organisms, the best part of us - roughly 70% - is water. And it needs to flow into us, out of us and inside us. We sweat water, we cry water, we digest with water, we think thanks to water and we pee water. Hundreds of litres of water go through a human kidney daily. How? Water molecules can cross cell membranes unassisted. However, such a form of transit cannot account for the huge amounts which are processed in a kidney. There must be another system. In the 1990s such a system was discovered: aquaporin. Aquaporins are proteins which are embedded within cellular or intracellular membranes and are high-tech channels specific to water molecules. And they are spread not only throughout the animal and the plant kingdom but also in bacteria.
Have you ever brought a glass of wine - or drinking water - to your lips and discovered a musty taste? Geosmin is what produces it. Geosmin is a germacranoid sesquiterpene or a trans-1,10-dimethyl-trans-9-decalol for the more chemically minded. Human taste buds are extremely sensitive to geosmin; the average person can detect 0.7 parts per billion! The chemical is produced by a number of microorganisms amongst which the mycelial soil bacteria Streptomyces, which have become invaluable in the medical field since they are an important source for naturally occurring antibacterial and antifungal agents as well as anticancer drugs and immunosuppressants.
Protein(s): Germacradienol synthase
Were it not for dynein, none of us would be here. There is an intriguing thought. Indeed, dynein is at the heart of a sperm's wriggle. Without it, there would be no race to the egg. And, what is more, an egg depends on the movement of cilia in its long journey from the Fallopian tubes to the womb. And it is dynein which makes cilia quiver. Dynein is in fact central to numerous movements in and outside a cell, such as mitosis, vesicular mobility, debris removal in the lungs and chemical transport in our nervous system. It is a molecular motor; fed on biological fuel - ATP - it creates movement. Much research has been done on this extraordinary protein because of its key role in sperm mobility and hence fertility.
Protein(s): Dynein 1-alpha heavy chain
How would you like to have wallpaper that changes colour according to the seasons? Imagine a warm ochre hue for the cold winter months and a fresh yellow tint for the hot summer months. Fantasising? No. Researchers in Madagascar have recently discovered a very peculiar protein from the epidermis of a rare species of chameleon, Chamaeleo differensis, which is in fact a pigment and takes on different hues depending on various environmental criteria. The protein was baptised - in an outburst of scientific originality - chameleonin.
Why remember when it is so important to forget? That sounds promising in a day and age when techniques to enhance your memory are as popular as a cup of tea. It is important not to forget your mother's birthday, where you live or how to dress, but it is very desirable to forget all the items you float past in a supermarket, the names you scan through in a phone directory and the sign posts you sweep past on your way home. We like to think that we are the masters of what we choose to remember and what we choose to forget. And no doubt, to a certain degree we are. But some initial filtering is done on the molecular level and for our own benefit. The understanding of the biochemistry involved in the process of learning, memory...and forgetfulness is still very much in its infancy, but we do know of one protein, protein phosphatase 1, which certainly seems to be at the heart of this primordial sift.
Protein(s): Protein phosphatase PP1
Castor oil was part of our grand parents' first-aid cabinets. Already widely used in ancient medicine, it became particularly popular in the 20th century and, like Vin Mariani1, it was the remedy to an endless list of human ails. Castor oil is derived from castor beans, which are the seeds of Ricinus communis - a plant native to tropical Southeast Africa grown worldwide today. Pleasing in appearance and seemingly harmless, a castor bean - like Dr Jekyll - has a nasty side to it. Besides the oily salve, the beans also produce a toxin known as ricin, which is left behind in the mash in the process of oil extraction. Ricin is lethal to men and has - like botulinum toxin2 and anthrax - been extensively studied in the event of its use as a bioweapon. Stalin's chief of the secret police, Lavrenti Beria, was summoned to develop poisons and assassination techniques, which were still in use well after his death. One notorious invention was the ricin-loaded platinum pellet which was fired into the thigh of the Bulgarian dissident Georgi Markov by way of an umbrella in London, in 1978.
Christmas and the New Year are almost forgotten. But has our body forgotten about the stuffing and the pudding, or the brandy butter and the chocolate truffles? Probably not. The cholesterol has been piling up slowly...and so have the chances of cardiovascular problems. We know that the levels of low-density lipoprotein (LDL) cholesterol in our blood can be an indicator of the potential for heart attacks. However, it looks as though a second molecule - C-reactive protein or CRP - is a far better indicator of cardiovascular disease. A study which has involved accompanying 28'000 women over a period of eight years, and previously 22'000 men over a shorter period, seems to point to a risk of heart attack when the levels of CRP are high - though the levels of cholesterol can be normal or even low.
Protein(s): C-reactive protein
Platypuses (Ornithorhynchus anatinus) are the only mammals that squirt venom. They do this from a mobile calcaneus spur situated on the inside of each hind limb. It is a sophisticated system. The spur itself is attached at its base to a small bone which can articulate; when needed it moves at a right angle to the limb ready to fire. Strangely, only male platypuses have spurs; female platypuses lose theirs during development. Platypus venom has been under close scrutiny since 1895 when two naturalists Charles J. Martin and Frank Tidswell made their first account. We know today that platypus venom is a cocktail of toxins, most of which is a mixture of proteins which resemble no other to date. These have been named the defensin-like proteins, or DLPs, because their three dimensional structure resembles that of an antimicrobial peptide known as beta-defensin.
Protein(s): Defensin-like peptide
While for many, shedding a few tears as they cut an onion is a fair price to pay considering the improvement it can make to a dish, there are some who would gladly do without. Cooks for one. Until recently, it was thought that what made the distinct flavour and aroma of onions was also what made you cry. So if you tampered with the lachrymatory factor, the onion's flavour and aroma would be dulled - which would not do. A small revolution has occurred, however. A team of Japanese scientists discovered, quite by chance, an enzyme which catalyses only the lachrymatory factor, and has been named lachrymatory factor synthase (LFS). Tampering with LFS may allow us to dry up the tears while preserving the taste.
Protein(s): Lachrymatory factor synthase
Humans are not the only mammals to indulge in cocaine. A particular strain of the bacterium Rhodococcus does too. In fact, it thrives on it. Not for the same reasons however. For this drug-consuming Rhodococcus, cocaine is the sole source of carbon and nitrogen. Scientists were led to it whilst rummaging in the soil, which surrounded the roots of coca plants, in their pursuit for a subtle drug detector. The bacterium revealed an enzyme - cocaine esterase - which is at the heart of cocaine metabolism. Cocaine esterase may well offer cocaine trackers a very fine drug sensor and could be used in emergency cases for cocaine overdose.
Protein(s): Cocaine esterase
Boil a lobster and its colour will go from blue to red. It is a known fact. And a fact that has been known for ages. What has not, however, is how a lobster's outside - which is blue - can turn red. Astaxanthin is the chromophore which lends a lobster its boiled orangey-red hue, as it does to many sea animals such as the pink flesh of salmon, the exoskeletons of crayfish - from where it was first identified - and shrimps, for instance. Surprisingly, astaxanthin is also the chromophore which gives lobsters their initial 'pre-boiled' blue-green colour. Why lobsters turn red in boiling water in the first place is a question which the American biologist George Wald (1906-1997) raised over half a century ago, and to which we now have an answer. What is more, as research progresses, it appears that astaxanthin could have beneficial effects on our health and that the structure of crustacyanin itself could be particularly interesting in the field of drug design.
There is more to the genetic code than meets the eye. We are acquainted with the dogma: 'One codon, one amino acid'. Life, however, has found a way of wriggling out of this straight jacket by using its stop codons as jokers. One example is given by our own mitochondrial DNA where the translational machinery recognises the UGA stop codon as tryptophan, and not as the classical stop codon as in the nucleus. Tryptophan though is an old-timer. As are the great majority of the now classical twenty amino acids which have been on the scene for over a century. Threonine was the last of the classics to be discovered in 1936. 1986, though, was another scoop year, when it was discovered that the UGA codon could produce a new amino acid altogether: selenocysteine. Selenocysteine, the 21st amino acid, is found in archaea, eubacteria and animals. Selenocysteine may just sound like a modified cysteine, but it is not because it has its own tRNA which is like granting it a passport. Similarly, in May 2002, the existence of a 22nd amino acid was reported: pyrrolysine.
Protein(s): Monomethylamine methyltransferase
In the 1900s, the Swiss physicist Auguste Piccard invented the bathyscaph, a submersible vessel for deep-sea observation. Long before though, spiders had already thought up a way of carrying out deep-pond observations using the same kind of strategy. A species of spider that lives in freshwater ponds throughout Europe weaves its own bathyscaph with silk. Bubbles of air keep the contraption afloat and a silk thread tethers it to a plant. Spiders use their silk for a number of purposes: besides catching their dinner by way of a woven web, some male spiders deposit sperm onto it and then offer the parcel to a female's genital opening. Silk is also used to wrap eggs in a silken cocoon or to hold offspring by means of a silk lifeline.
Protein(s): Dragline silk fibroin
What is it in a cell that drives it to become one type of cell rather than another? Or for that matter, what is it in a cell that summons it not to budge? It is the fascinating world of cell fate, one of the most intriguing questions developmental biologists have been asking themselves for centuries now. The blue-green algae cyanobacteria Anabaena is a perfect illustration of one model which has been on the scene for some time: cell differentiation occurs thanks to the diffusion of molecules, which creates a cell gradient.
Protein(s): Heterocyst inhibition signaling peptide
There is not much we would hear without our cochlea. Our what? The cochlea is a part of our inner ear and looks remarkably like a snail's shell. This minute masterpiece of mammal physiology - only a few millimetres large - acts as a sound amplifier and without it the noises which surround us would be mere fuzz. And how does it amplify sound? Amongst the many controversial theories, there is one which is based on the behaviour of quite a singular protein: prestin. Why singular? Because prestin is the only cellular motor to date which does not require biological energy - such as ATP - to function.
Max Perutz (1914-2002) solved the molecular structure of haemoglobin in 1960. It had taken him the best part of 25 years. He arrived at the Cavendish laboratory in Cambridge in 1936 eager to start a PhD. In those days, there was marked excitement about the possibility that X-ray photography of protein crystals could deliver the atomic arrangement of proteins. Two crystals were presented to Perutz: one of chymotrypsin and another of haemoglobin. The chymotrypsin crystals grew in such a manner that they were too complex to decipher so Perutz turned to the haemoglobin crystals which he felt would be easier to solve. Haemoglobin was also a choice candidate: it has an important physiological role, supplies are never scarce and it forms crystals easily. And little did Perutz know that this macromolecule would keep him busy for the rest of his life.
Scientists discovered the use of Oldenlandia affinis as an oxitocic agent in Africa, in the 1960s. O. affinis is a perennial weed with a woody root and blue-violet flowers, and is found in the tropical zones of Africa and western Asia. There are 196 different species of Oldenlandia and their use in traditional medicine is as widespread as their geography. India uses many of the different species in as many different drugs. However, it was the uteroactive activity of a green brew, Kalata-Kalata, given to African women during labour that first triggered an interest. The decoction was made from a handful of dried O. affinis boiled in about a litre of water. Women about to give birth were either given the tea to sip or it was directly applied per vaginum; contractions became stronger and delivery was shortened. What was the nature of the uteroactive agent? The green potion was whipped to a laboratory and the main uteractive agent turned out to be a small protein named after the traditional medicine from which it was extracted: kalata B1.
Protein(s): Kalata B1
It was a bout of sausage poisoning which led to the discovery of a protein now known as botulinum toxin. During the Napeolonic Wars, the Dukedom of Würtemberg in Stuttgart observed an increase in human deaths due to food intoxication. Smoked sausages seemed to be at the heart of the problem and the poison was subsequently termed sausage poison. It was the medical officer and poet Justinus Kerner (1786-1862) who first suspected poison of biological origin. The clinical symptoms added to his own experimental observations - he had fed bad sausage to various animals as well as to himself - led him to believe that the poison interfered with the motor and autonomous nervous signal transmission system. 'The nerve conduction is brought by the toxin into a condition in which its influence on the chemical process of life is interrupted.' Indeed, patients experienced a progressive paralysis from the cranium down which would end in death by suffocation following progressive difficulties in breathing. Kerner, however, did not know what the nature of the toxin was.
Protein(s): Botulinum neurotoxin
We all sweat. Which is just as well because, generally speaking, the loss of body fluids is essential to our well-being. It rids us of a certain number of physiological impurities. Our skin - the material through which we sweat - is an organ per se, the largest one we carry around and a particularly complex one. It is a spaghetti junction of blood vessels, a harbour for nerve endings, a workshop for pigmentation and a field of sweat glands, oil glands and hair follicles. And that is not all. Our skin has also been called our 'third kidney'. Indeed, waste seeps through it daily: sodium, chloride, potassium, magnesium, calcium, urea, ammonia, uric acid - which is what tastes salty on the skin once all the water has evaporated - but also toxic metals such as copper, lead, zinc and mercury offered to us by way of environmental pollution. Amongst all this body garbage, however, is a protein known as dermcidin, which is not debris but an antibiotic peptide. Here is medicine we actually perspire.
There are four basic tastes...so we are told. Any other taste is a mere combination of these four. Which four? Bitter, sweet, sour and salty. However, a fifth taste - of Asian heritage - is seeping into the Western World and gaining fast recognition: the umami (oo-mom-ee) taste. A taste qualified as meaty or savoury. All these tastes are recognised as such thanks to specific taste receptors and our brain. Some tastes are proteins and are already used in the industry as natural sweeteners, for example. Among such taste proteins, there is one in particular - miraculin - which lacks taste completely when absorbed on its own but has the power of modifying a disagreeable taste into a pleasant one.
As children, we were told that milk was good for our bones and teeth. No one told us though how essential this natural opaque white liquid has been for humans in the past millennia. Cow's milk is about 88% water, 3.3% protein and the rest is carbohydrate and fat. Caseins are the major milk proteins, and the yellowish gelatinous mixture that forms the milk curd is packed full of them. Curds were used by the Ancient Egyptians as a fixative for pigments in wall paintings and, since the Renaissance, casein has been used as a binder for paints. A particularly good adhesive for wood, casein glue was already used in the 18th century in the construction of chalets in Switzerland and was particularly popular for the construction of the wooden frame parts of aircraft during World War I. However, casein glue absorbs moisture, which more often than not results in the growth of fungal mould, which in turn weakens the adhesiveness of the glue.
In China, there is an old legend which says that Buddha (?563-483 BC) slit his eyelids off in a struggle to stay awake. They fell to the moist ground below, from which grew a red flower, the opium poppy. Opium was used as a narcotic as early as 4'000 BC in Sumerian and European cultures. In 1753, the Swedish botanist Linnaeus classified the poppy as Papaver somniferum, a sleep-inducing plant. Would it not be handy to discard one's eyelids to fight off somnolence? Patients suffering from narcolepsy would certainly agree. Narcolepsy is an inconvenient sleep disorder where those afflicted with it fall asleep at any time of the day. Since 1998, much research has been made in this field following the discovery of a small protein that has a role in our state of wakefulness: hypocretin.
'Zookeepers are trained to inspect and monitor service portal perimeters before opening and while inserting their arms. Always use long forceps to change food dishes or remove debris.' Against which animal could these warnings be for? A ferocious feline? A vicious viper? A ruthless rodent? Nope. An ant. Paraponera clavata, otherwise known as the bullet ant. Bullet ants are jet black and about 25mm in length. They are amongst the most primitive of the ant species: their social organisation is envied by no other species of ant and their queen is barely larger than her subjects. Princess Bala in the famous movie Antz was named so after the Spanish 'bala' meaning 'bullet'. And the bullet ant is also known as the bala ant for the same reason.
Gloves can be dangerous. Yes, but so can rubber soles, condoms, swimming caps, various medical appliances and even toys. And the offender is latex. Latex is the milky fluid tapped from rubber trees, which - following a series of processes - produces the different types of rubber used by the commercial, medical, transportation and defence industries. To date, natural rubber is used in over 40'000 products. And it is nothing new. Ancient Mesoamerican societies were already harvesting latex in 1600 BC from the Panama rubber tree or Castilla elastica. Not only were they harvesting it but they also processed it in order to obtain a pliable bouncy rubber, by adding the sap extracted from a second plant - a species of morning glory vine or Ipomoea alba - which grows on C.elastica. With the rubber, they fashioned hollow rubber figurines, wide rubber bands and bouncy balls with which they are said to have played violent games. Liquid rubber was used for medicines and paint.
Protein(s): Small rubber particle protein
Beekeeping is one of the healthiest professions they say. Apparently, apiarists have fewer illnesses than most other humans. They never seem to have cancer or arthritis, or other kinds of immune disease and they even live longer. Though one could rightly argue whether the number of beekeepers in the world represents a significant sample of the human population, it is a fact that the healing properties of honey, and bee products in general, have been popular in a number of civilisations for thousands of years.
A bulb emitting light seems quite natural but...a jellyfish? As early as the first century, Pliny described the light of Pulmo marinus, now known as Pelagia noctiluca, a purple jellyfish. Bioluminescence is a spectacular phenomenon which predates by far the electric bulb and on which much research has been done since the 18th century. Jellyfish have been squeezed through cheesecloth, rubbed onto countless surfaces and submitted to electrical stimuli; all for the sake of a green glow. Jellyfish are not the only species to luminesce; corals, sea gooseberries, fish, bacteria, toadstools, plankton, fungus, glow-worms and many more also do. And the glow is not only green but for some, yellow, red, cyan or blue.
Protein(s): Green fluorescent protein (GFP)
Fat is not a passive depository of grease. Fat is, in effect, quite precious and fulfils multiple functions in our bodies. Now there's a thought in a day and age where the slightest lipid bump is deemed ungracious! It cushions our fingertips and eye sockets, and acts as a shock absorber in our knee joints and heels. It blankets our internal organs and lines our bellies, seals perforations within internal organs and may well play a role in local immune responses. Adolescents need fat to mature sexually, young women need fat to cope with pregnancy and, in older women, fat protects bones from the effects of menopause.
Insulin should have been named protein of the 20th century. It was one of the first proteins to be crystallised in pure form, in 1926. It was the first protein to be fully sequenced in 1955, the first protein to be chemically synthesized in 1958 - though in insufficient quantities to be produced commercially - and the first human protein to be manufactured by way of biotechnology in 1979. Indeed, insulin has been on the forefront of Science for more than half a century. And why? Because of diabetes.
How long can you stay awake? In 1988, Robert McDonald from California managed to trick his sleep for 18 days, 21 hours and 40 minutes. But what exactly was he tricking? Two thousand years ago, it was believed that drowsiness was due to stomach vapours - themselves the result of digestion - which rose to the brain, condensed there and blocked the pores. The head was thus cut off from the rest of the body and sleep ensued. This mechanical concept of sleep survived for almost two millennia. It was only in the second half of the 19th century that a more subtle approach was made, separately, by Kuniomi Ishimori in Japan and Henri Piéron in France. What if sleep were the result of "fatigue substances" that are accumulated during the period of wakefulness and dissipated while sleeping? The hypothesis had its ups and downs. However, in the 1960s, Marcel Monnier and his associates in Switzerland discovered the existence of a very small peptide that seemed to have sleep-inducing effects: the Delta Sleep-Inducing Peptide or DSIP.
Protein(s): Delta sleep-inducing peptide
When you punch a hole in a tyre, it deflates. Besides being simple, it is a strategy that is used by a number of plants and animals as a means of defence. To this end, they make use of antimicrobial peptides which alter the enemy's cellular membrane in such a way that the inside leaks out, or the outside leaks in, thus causing cell death. Antimicrobial peptides have been discovered in all kinds of organisms, from fruit flies to horseshoe crabs, and honeybees to humans. It is a rapid immune response to microbes that surround us daily. When a frog swallows a fly, it also ingurgitates an army of microbes, which have to be eliminated or, at least, whose growth rate has to be checked. Magainins, from the Hebrew "magain" meaning shield, do just this and they were the first antimicrobial peptides to have been described.
Romeo chose to sing softly to Juliette after dusk, on a warm summer's night. And the onset of daylight, like the blowing of a cool breeze, would only have interfered with his lyrical hum. Drosophila has no such qualms when playing a serenade to the loved one. Neither a change in light nor a change in temperature has any effect on the fruit fly's courtship song. What is Drosophila's light- and temperature-insensitive love song? Put bluntly, it is a case of acoustic communication with an end to mate. Just like Romeo.
Protein(s): Period circadian protein
The antifreeze you load your window screen with on a cold frosty morning is nothing new. Antarctic marine fish devised a way to prevent themselves from freezing to death long before the Model T Ford had been thought up. While some organisms use sodium chloride, potassium, calcium, urea, free amino acids or glycerol to survive harsh conditions, the Antarctic notothenioids - such as the yellowbelly rockcod - have developed sophisticated ways of coping with polar conditions by producing a form of high-class antifreeze: antifreeze glycopeptides. These antifreeze proteins are more than 100 to 200 times more effective than any other type of antifreeze molecule and are found in most notothenoid body fluids, which is fortunate since these fish spend their lives in ice-laden waters. Fish that live in more northern temperate waters produce antifreeze proteins on a seasonal basis.
Protein(s): Antifreeze glycopeptide polyprotein
The human ear is an elegant and intricate organ that consists of an outer, an inner and a middle ear, and converts mechanical signals into electrical signals with great precision. The outer ear is relatively simple in structure and functions as a sound-collecting funnel which directs sound waves to the middle ear. The middle ear transmits sound waves to the inner ear via three small bones: the malleus, the incus and the stapes. The inner ear is the ear's boiler room; this is where sound waves are processed into electrical signals and sent - via the auditory nerve - to the brain.
Protein(s): Cochlin protein
Harpoons are not only man's invention. Paramecium has also developed quite a sophisticated harpoon-like means of defence: trichocysts. The Algerian protozoologist Emile Maupas (1842-1916) had already observed trichocysts through a light microscope in the 19th century and noted an "explosion so instantaneous [at the cell's surface] and so fast that it was quite impossible to follow the transformation of the spindle-shaped rod into a fine needle".
Protein(s): Trichocyst matrix protein
Mussels live in turbulent niches in the intertidal zone of the ocean. Their survival depends on their ability to attach to rocks. They adhere tightly to surfaces under water using a structure at the base of the foot, which consists of a bundle of threads: the byssus. At the end of each thread is an adhesive plaque that contains water-resistant glue which enables mussels to anchor to solid surfaces.
Protein(s): Adhesive plaque matrix protein
Had you ever wondered why strawberry ice creams are sometimes so pink? Food colouring is the answer. Natural pigments are widely used in the food industry and have been studied extensively. Long before the art of food colouring, however, there existed Nature's own art of plant colouring. And its palette is rich. Take betalains for example. Betalains are natural pigments synthesized exclusively in plants of the order Caryophyllales - where you find spinach and beetroot but also purslane, cacti and bougainvillea - and, surprisingly, in toadstools of the order Amanita.
Protein(s): DOPA 4,5-dioxygenase