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

Abstract

Procollagen assembly occurs within the endoplasmic reticulum, where the C-propeptide domains of three polypeptide α-chains fold individually, and then interact and trimerise to initiate folding of the triple helical region. This highly complex folding and assembly pathway requires the co-ordinated action of a large number of endoplasmic reticulum-resident enzymes and molecular chaperones. Disease-causing mutations in the procollagens disturb folding and assembly and lead to prolonged interactions with molecular chaperones, retention in the endoplasmic reticulum, and intracellular degradation. This review focuses predominantly on prolyl 4-hydroxylase, an essential collagen modifying enzyme, a..