Structural correlations in the family of small leucine-rich repeat proteins and proteoglycans.
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.
McEwan
Paul A
PA
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK.
Scott
Paul G
PG
Bishop
Paul N
PN
Bella
Jordi
J
D000595:Amino Acid Sequence; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011509:Proteoglycans