Chapter 9 Posttranslational processing of collagens

Summary Collagen synthesis is characterized by the presence of an unusually large number of cotranslational and posttranslational modifications, many of which are unique to collagens and a few other proteins with collagen-like amino acid sequences. The posttranslational processing of a fibrillar collagen can be regarded as occurring in two stages: intracellular modifications, together with synthesis of the polypeptide chains, result in the formation of triple-helical procollagen molecules, and extracellular processing then converts these molecules into collagens and assembles the collagen molecules into stable, crosslinked fibrils. The processing of a nonfibrillar collagen is basically similar to that of a fibrillar collagen, except that it may not involve a procollagen intermediate and the extracellular supramolecular assemblies are not fibrils. These processing reactions require at least nine specific enzymes and several nonspecific ones. The intracellular modifications require three specific hydroxylases that convert certain proline and lysine residues to 4-hydroxyproline, 3-hydroxyproline and hydroxylysine, and two specific glycosyltransferases that convert some of the hydroxylysine residues to galactosylhydroxylysine and some of the galactosylhydroxylysine residues to glucosylgalactosylhydroxylysine. The extracellular modifications require two specific procollagen proteinases, one to cleave the N-terminal propeptide and the other the C-terminal propeptide, and lysyl oxidase, which initiates crosslink formation by catalyzing oxidative deamination of certain lysine and hydroxylysine residues to reactive aldehyde derivatives. One of these enzymes, procollagen N-proteinase, has two collagen type-specific isoenzymes, whereas in all the other specific posttranslational modifications a single enzyme appears to act on all the collagen types. Most of these nine enzymes are now well characterized and three of them have been cloned. Detailed data are also available on the properties and functions of most of the posttranslational modifications.