Procollagen folding and assembly: The role of endoplasmic reticulum enzymes and molecular chaperones

Procollagen assembly occurs within the endoplasmic reticulum, where the C-p ropeptide domains of three polypeptide alpha-chains Sold individually, and then interact and trimerise to initiate folding of the triple helical regio n. This highly complex folding and assembly pathway requires the co-ordinat ed action of a large number of endoplasmic reticulum-resident enzyme and mo lecular chaperones. Disease-causing mutations in the procollagens disturb f olding and assembly and lead to prolonged interactions with molecular chape rones, retention in the endoplasmic reticulum, and intracellular degradatio n. This review focuses predominantly on prolyl 4-hydroxylase, an essential collagen modifying enzyme, and HSP47, a collagen-specific binding protein, and their proposed roles as molecular chaperones involved in fibrillar proc ollagen folding and assembly, quality control, and secretion.