proprotein

A proprotein is a precursor form of a protein that is synthesized in an inactive or less active state and requires proteolytic processing to become mature and functional. Proproteins include enzymes produced as zymogens, as well as hormones and signaling molecules that contain inhibitory propeptides which must be removed or rearranged to generate the active form.

Activation of proproteins typically occurs through proteolytic cleavage, often within the secretory pathway or at sites of action after secretion. Specific proteases, such as proprotein convertases (for example furin and related PCSK enzymes), recognize defined cleavage motifs and excise propeptides to yield active enzymes, hormones, or signaling peptides. In many cases, additional maturation steps, such as disulfide bond rearrangements or glycosylation, accompany or follow this cleavage.

Examples of proproteins include pepsinogen, the precursor of the digestive enzyme pepsin; trypsinogen, the precursor of trypsin; proinsulin, which is processed to insulin; proopiomelanocortin (POMC), which yields ACTH and several peptide hormones; prothrombin, the precursor of thrombin; and proBDNF, the precursor of brain-derived neurotrophic factor. These examples illustrate how proprotein processing enables regulated activation of enzymes and signaling molecules.

The proprotein strategy provides spatial and temporal control over biological activities, preventing premature action and allowing tissue- or condition-specific activation. Malfunctions in proprotein processing or the enzymes that effect activation can contribute to disease, including metabolic, endocrine, and neurodegenerative disorders.

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