title: Structural and functional analysis of two small leucine-rich repeat proteoglycans, fibromodulin and chondroadherin.
abstract: The small leucine-rich proteoglycans (SLRPs) are important regulators of extracellular matrix assembly and cell signalling. We have determined crystal structures at ~2.2Å resolution of human fibromodulin and chondroadherin, two collagen-binding SLRPs. Their overall fold is similar to that of the prototypical SLRP, decorin, but unlike decorin neither fibromodulin nor chondroadherin forms a stable dimer. A previously identified binding site for integrin α2β1 maps to an α-helix in the C-terminal cap region of chondroadherin. Interrogation of the Collagen Toolkits revealed a unique binding site for chondroadherin in collagen II, and no binding to collagen III. A triple-helical peptide containing the sequence GAOGPSGFQGLOGPOGPO (O is hydroxyproline) forms a stable complex with chondroadherin in solution. In fibrillar collagen I and II, this sequence is aligned with the collagen cross-linking site KGHR, suggesting a role for chondroadherin in cross-linking.
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: Paracuellos
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kalamajski
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Bonna
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bihan
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom. Electronic address: e.hohenester@imperial.ac.uk.
authors.forename: Erhard
authors.initials: E
authors.lastname: Hohenester
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D003553:Cystine / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D000071235:Fibromodulin / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D012996:Solutions
chemical_list: D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D012996:Solutions; C088980:chondroadherin; D000071235:Fibromodulin; D003553:Cystine
keywords: Collagen; Leucine-rich repeat; X-ray crystallography