prepropeptides

Prepropeptide is the initial translation product of a gene encoding a secreted or organellar peptide that contains both a signal sequence (the pre region) and a propeptide region (the pro region). The pre region targets the polypeptide to the secretory pathway and is cleaved off soon after entry into the endoplasmic reticulum; the pro region facilitates proper folding and trafficking and is typically removed later to yield the mature bioactive peptide. The mature peptide may be produced as one or more products after proteolytic processing of the pro region.

Processing: In the secretory pathway, the pre sequence is removed by signal peptidase in the ER. The resulting propeptide contains specific cleavage sites recognized by prohormone convertases and other proteases, which excise the mature peptide and may generate additional fragments. Final maturation may involve further trimming and post-translational modifications such as disulfide bond formation, amidation, or glycosylation. The mature peptides are often stored in secretory granules and released in response to stimuli.

Examples: The classic example is preproinsulin, which is translated as preproinsulin; after signal peptide removal, proinsulin is processed to insulin and C-peptide. Another example is preproglucagon, which yields glucagon and related peptides such as GLP-1. A third example is preprovasopressin, which yields vasopressin and its associated carrier protein neurophysin II.

Notes: The term prepropeptide emphasizes the combined pre and pro regions; some literature uses prepropeptide to refer to the entire precursor, while propeptide denotes just the region after signal peptide. Not all prepropeptides yield single mature products; alternative processing can generate multiple peptides with distinct activities. The concept is central to understanding hormone and neuropeptide biosynthesis.