Molecular characterisation of integrin-procollagen C-propeptide interactions

Darryl Davies, Danny S. Tuckwell, David A. Calderwood, Susan A. Weston, Masarahu Takigawa, Martin J. Humphries

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The carboxyl-terminal propeptide of type I procollagen (CPP-I) plays a key role in regulation of collagen fibrillogenesis, and may exert feedback control of collagen biosynthesis. We have previously shown that CPP-I is a ligand for the integrin α2β1 [Weston, S. A., Hulmes, D. J. S., Mould, A. P., Watson, R. B. and Humphries, M. J. (1994) Identification of the integrin α2β1 as a cell surface receptor for the C propeptide of type I procollagen, J. Biol. Chem. 269, 20 982-20986] suggesting that some of the phenotypic effects of C-propeptides may be mediated by adhesion receptors. Here we have extended this work to study the molecular basis of this interaction. We have broadened the ligand range by demonstrating that the C-terminal propeptide of type II procollagen supports α2β1-mediated binding of NHS human fibroblasts in cell attachment assays. Also, we have used function-blocking antibodies in cell attachment and solid-phase binding assays with purified integrin to expand the CPP-I receptor family, showing that integrin α1β1 is also a receptor for CPP-I. Integrin α-subunit A-domains are known to be major ligand binding sites and recombinant α1 and α2 subunit A-domains were able to bind CPP-I. Finally we have shown that peptides corresponding to potential integrin-binding sequences in CPP-I do not mediate integrin-CPP-I adhesion. Taken together, these studies indicate that the interactions between C-propeptides and integrins are more numerous than previously reported, that C-propeptides are a new class of molecule which bind to A-domains, and that the integrin-C-propcptide interaction does not utilise established peptide motifs.

Original languageEnglish
Pages (from-to)274-282
Number of pages9
JournalEuropean Journal of Biochemistry
Volume246
Issue number2
DOIs
Publication statusPublished - 1997

Keywords

  • Collagen
  • Integrin
  • Propeptide
  • VSFA domain

ASJC Scopus subject areas

  • Biochemistry

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