Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans

Paul A. McEwan, Paul G. Scott, Paul N. Bishop, Jordi Bella

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The family of small leucine-rich repeat proteins and proteoglycans (SLRPs) contains several extracellular matrix molecules that are structurally related by a protein core composed of leucine-rich repeats (LRRs) flanked by two conserved cysteine-rich regions. The small proteoglycan decorin is the archetypal SLRP. Decorin is present in a variety of connective tissues, typically "decorating" collagen fibrils, and is involved in important biological functions, including the regulation of the assembly of fibrillar collagens and modulation of cell adhesion. Several SLRPs are known to regulate collagen fibrillogenesis and there is evidence that they may share other biological functions. We have recently determined the crystal structure of the protein core of decorin, the first such determination of a member of the SLRP family. This structure has highlighted several correlations: (1) SLRPs have similar internal repeat structures; (2) SLRP molecules are far less curved than an early model of decorin based on the three-dimensional structure of ribonuclease inhibitor; (3) the N-terminal and C-terminal cysteine-rich regions are conserved capping motifs. Furthermore, the structure shows that decorin dimerizes through the concave surface of its LRR domain, which has been implicated previously in its interaction with collagen. We have established that both decorin and opticin, another SLRP, form stable dimers in solution. Conservation of residues involved in decorin dimerization suggests that the mode of dimerization for other SLRPs will be similar. Taken together these results suggest the need for reevaluation of currently accepted models of SLRP interaction with their ligands. © 2006.
    Original languageEnglish
    Pages (from-to)294-305
    Number of pages11
    JournalJournal of Structural Biology
    Volume155
    Issue number2
    DOIs
    Publication statusPublished - Aug 2006

    Keywords

    • Collagen
    • Crystal structure
    • Decorin
    • Leucine-rich repeats
    • Opticin
    • Proteoglycans

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