Procollagen

Procollagen is the intracellularly produced, soluble precursor of collagen, the main structural protein of connective tissues. It consists of three pro alpha chains forming a triple helix with nonhelical N- and C-terminal propeptides that prevent premature fibril formation inside cells. Procollagen is synthesized by fibroblasts, osteoblasts, chondrocytes, and other collagen-secreting cells.

During synthesis in the endoplasmic reticulum, the collagen alpha chains undergo post-translational modifications: hydroxylation of proline and lysine residues, glycosylation of hydroxylysine, and formation of stabilizing disulfide bonds in the propeptides. The triple helix is assembled and then secreted as a soluble procollagen molecule.

Outside the cell, specific proteases remove the N- and C-terminal propeptides to generate mature tropocollagen units, which subsequently assemble into long fibrils. Enzymatic cross-linking by lysyl oxidase strengthens the fibrils, forming mature collagen fibers that integrate into the extracellular matrix.

Types and genetics of procollagen are primarily associated with the fibrillar collagens types I, II, and III. These correspond to genes such as COL1A1/COL1A2 (type I), COL2A1 (type II), and COL3A1 (type III). Defects in procollagen processing or maturation can contribute to connective tissue disorders, including Ehlers-Danlos syndrome and osteogenesis imperfecta. Vitamin C deficiency impairs hydroxylation steps, affecting collagen stability.

Processing of procollen and maturation of collagen involve enzymes such as procollagen N-proteinases (for example ADAMTS-2) and C-proteinases (such as BMP-1), along with enhancers like PCOLCE that facilitate extracellular maturation.