Our bodies digest and produce waste continuously. And it is happening at every molecular level. The most obvious digestive pathway we know of is the one we launch by inserting something into our mouth, chewing it, swallowing it and discharging the debris once it has been through the whole degradation process. Mouths are not the only things that open and shut to initiate digestion. On a far smaller scale, some proteins do it too. Presequence protease – or PreP – is one.
PreP is a protease found both in mitochondria and chloroplasts . Proteins, whose presence is requested in either organelle, are led there thanks to peptides known as target peptides which act as address tags. Their destination reached, the target peptides are removed from the proteins much in the way you would separate a letter from its envelope. The inconvenience is that the envelopes pile up unless you throw them out. That is where PreP comes in. PreP gets rid of the target peptides – which would otherwise poison the organelle – and degrades them.
PreP acts a little like a molecular vacuum – passive in recognizing the waste but active once it is in its guts. It is a homodimer, whose two subunits are bound by, and revolve around, a hinge. Unless active, the protease floats around with its jaws wide open. Thus the chamber inside is open to target peptides that will recognize a specific site. The act of binding induces a conformational change in the protease’s structure: the gap to the chamber is closed and amino acids, which are hundreds of residues apart, are brought closer to one another to create the active site. And it is with its mouth closed that the protease degrades the target peptides. Once digested, the link between the distant residues in the active site is probably broken. As a consequence and most likely by way of electrostatic forces, the gap opens and the digested peptides are released.
Besides the astonishing waste-removing abilities of PreP, such a protease could also prove to be of great medical interest. In truth, this particular protease is capable of degrading not only target peptides but also a number of other peptides such as amyloid-β for instance, whose existence is related to mitochondrial toxicity and Alzheimer’s disease. A question arises: if PreP can trap and degrade more than one peptide, could it not catch hold of some that it shouldn’t? Apparently not. The size of the gap – as the chamber formed inside the protease – is calculated so that larger molecules such as folded proteins for example cannot enter and be damaged. Like us, PreP is choosy. You wouldn’t pop any old thing into your mouth, would you?