preprotein

A preprotein, also called a precursor protein, is an immature protein that includes extra amino-terminal sequences that are removed during maturation to yield the active, mature protein. Preproteins arise as part of regulated protein biosynthesis for secretion, localization to organelles, or control of activity.

In many eukaryotic cells, preproteins destined for secretion or for residence in the endomembrane system begin with a signal peptide at the N-terminus. This signal directs ribosome targeting to the endoplasmic reticulum via the signal recognition particle and its receptor. The signal peptide is typically cleaved by signal peptidase as the protein enters the secretory pathway. Some preproteins also contain propeptides that suppress catalytic activity or assist folding; these propeptides are removed by proteases such as proprotein convertases in the Golgi.

Other preproteins carry transit or targeting peptides for organelles such as mitochondria or chloroplasts. After import into the organelle, these sequences are removed by specific processing peptidases, yielding the mature protein that functions within the organelle.

In bacteria, preproteins with N-terminal signal peptides are recognized by the signal recognition particle and translocated across the cytoplasmic membrane through the Sec pathway. Signal peptidases then remove the signal sequence, and the mature protein folds and matures in the periplasm or is integrated into the membrane.

Classic examples include preproinsulin. After the signal peptide is removed in the secretory pathway, the remaining molecule is proinsulin, which is subsequently processed to mature insulin by removal of the C-peptide. The preprotein concept is central to understanding protein targeting, secretion, and maturation in many biological systems.