The importance of proline residues in the structure, stability and susceptibility to proteolytic degradation of collagens

Abstract

Collagens are among proteins that undergo several post-translational modifications, such as prolyl hydroxylation, that occur during elongation of the nascent chains in the endoplasmic reticulum. The major structural collagens, types I, II and III, have large, uninterrupted triple helices, comprising three polyproline II-like chains supercoiled around a common axis. The structure has a requirement for glycine, as every third residue, and is stabilized by the high content of proline and 4-hydroxyproline residues. Action of prolyl hydroxylases is critical. Spontaneous or targeted genetic defects in prolyl hydroxylases can be lethal or result in severe osteogenesis imperfecta. Prolines, as determinants of substrate specificity and susceptibility, also play a role in degradation of collagen by collagenolytic matrix metalloproteinases (MMPs). Targeted mutations in mice in the collagenase cleavage domain have profound effects on collagen turnover and the function of connective tissues. Prolines are thus critical determinants of collagen structure and function.