Molecular recognition in procollagen chain assembly

Abstract

Recent advances in the understanding of the molecular recognition events occurring during the assembly of procollagen during biosynthesis have come from the use of a semi-permeabilized cell-system that reconstitutes the initial steps of chain assembly as they would occur in the endoplasmic reticulum of an intact cell. This has enabled a number of key questions concerning the molecular determinants of procollagen assembly to be addressed. In particular, the recognition events underlying the initial association of individual procollagen chains have been investigated, resulting in the identification of the key residues involved within the C-propeptide of fibrillar collagens. Similarly, the role of inter-chain disulfide bond formation in chain recognition and assembly has been investigated, along with the role of the C-propeptide, C-telopeptide and proline hydroxylation in helix nucleation, alignment and propagation. The results from these studies point to a two-stage recognition event, i.e., association of the chains driven by residues within the C-propeptide followed by nucleation and alignment of the helix driven mainly by sequences present at the C-terminal end of the triple helical domain.