preprokollagen

Preprokollagen, often referred to as preprocollagen in Swedish contexts, is the initial translation product of collagen gene transcripts. It comprises an N-terminal signal peptide (the “pre”) that directs the polypeptide to the endoplasmic reticulum and non-helical N- and C-terminal propeptide regions (the “pro”) that regulate subsequent assembly. The presence of these segments distinguishes the prepro form from mature collagen and from the later procollagen intermediate.

During synthesis, the signal peptide is cleaved in the endoplasmic reticulum to form procollagen. The polypeptide chains undergo post-translational modifications, including hydroxylation of proline and lysine residues and glycosylation of hydroxylysine, aided by vitamin C–dependent enzymes. The three α chains assemble into a triple helix, stabilized by disulfide bonds in the C-terminal region, yielding procollagen.

Procollagen is secreted into the extracellular matrix, where extracellular proteases remove the N- and C-propeptides to produce tropocollagen. Tropocollagen molecules then self-assemble into collagen fibrils, which are crosslinked by lysyl oxidase to form mature, load-bearing fibers in connective tissues.

Genes encoding collagen chains (such as COL1A1, COL1A2, and others) give rise to preprokollagens that follow this biosynthetic pathway. Proper processing and post-translational modification are essential for the structural integrity of skin, bone, cartilage, tendons, and other connective tissues.

Defects in collagen synthesis, modification, or processing can contribute to connective tissue disorders, including osteogenesis imperfecta and certain forms of Ehlers-Danlos syndrome; vitamin C deficiency (scurvy) impairs hydroxylation and collagen stability.