prodomain

A prodomain is a segment of a precursor protein that is typically removed during maturation to yield the mature, active protein. Prodomains are common in secreted and membrane-associated proteins and can serve several roles in biosynthesis and regulation.

Functions of prodomain regions include assisting proper folding, promoting correct trafficking through the secretory pathway, and governing the timing, location, and mechanism of activation. In many enzymes, the prodomain acts as an intrinsic autoinhibitor that blocks the active site; proteolytic cleavage removes the prodomain to generate an active enzyme, a process known as proprotein processing.

Activation mechanisms vary by protein family. Proteolytic cleavage by specific proteases such as proprotein convertases (for example furin and related PCSK enzymes) in the secretory pathway or later extracellular proteases often converts inactive zymogens or proproteins into their active forms. In some cases, the prodomain remains noncovalently bound after processing, forming latent or inert complexes that require additional cues for activation.

Examples span several protein categories. Digestive enzymes such as trypsinogen, chymotrypsinogen, and proelastase carry prodomains that prevent activity until cleavage. Proinsulin includes a C-peptide region that is removed to produce mature insulin. Growth factors in the TGF-β family are synthesized with a latency-associated peptide that acts as a prodomain, maintaining the mature factor in an inactive state until activation occurs.

Overall, prodomain sequences are integral to the controlled maturation and regulation of many proteins, influencing folding, stability, localization, and timely activation. See also proprotein convertases, zymogens, and latency-associated peptide.