Propeptide

A propeptide is a segment of a precursor protein that is cleaved off to produce the mature polypeptide. Propeptides can act as intramolecular chaperones to assist folding, prevent premature activity, or direct trafficking through the secretory pathway. In some cases, the propeptide itself is released and functions as a separate bioactive peptide.

Most propeptides are removed by proteolytic processing at specific cleavage sites, often by proprotein convertases within the secretory pathway or by extracellular proteases after secretion. The timing and location of cleavage determine the composition and activity of the mature product. The presence of a propeptide is a common feature in many hormones, enzymes, and structural proteins produced as part of larger precursors.

Examples include proinsulin, where the C-peptide is excised to yield mature insulin and is co-secreted with it; the C-peptide can serve as a biomarker of insulin secretion. In collagen biosynthesis, N- and C-propeptides facilitate proper triple-helix formation and are removed by extracellular proteases to allow mature collagen fibril assembly. In zymogens such as pepsinogen and trypsinogen, propeptides keep the enzymes inactive until activation. Propeptides can also enable multiple mature products from a single precursor through alternative processing, contributing to protein diversity.