prodomains

A prodomain, also called a propeptide, is a segment of a protein that is required for proper folding, processing, and regulation of maturation. Prodomains are especially common in secreted and membrane-associated proteins, including many proteases synthesized as inactive precursors (zymogens), as well as certain growth factors and cytokines. The prodomain is typically located adjacent to the mature domain and often contains signals that facilitate correct folding and trafficking of the protein.

In proteases, the prodomain usually blocks access to the enzyme’s catalytic site, maintaining latency until the protein reaches the correct cellular compartment or extracellular environment. Activation occurs upon proteolytic cleavage or autocatalysis, releasing the mature enzyme. Prodomains can also function as intramolecular chaperones that assist folding and stability, and in some cases they influence subcellular localization or substrate specificity.

Examples include pepsinogen and trypsinogen, which are activated by proteolytic processing to become active digestive enzymes; and the latency-associated peptide (LAP) of transforming growth factor beta (TGF-β), which forms a noncovalent complex with the mature growth factor to keep it inactive until extracellular activation. Prodomains are also found in various metalloproteases, such as members of the ADAM family, where they contribute to proper folding, trafficking, and regulation of protease activity.

In biotechnology, prodomain sequences are sometimes used to enhance expression, folding, or secretion of recombinant proteins and may be removed to yield the mature product.