Structural and functional analysis of two small leucine-rich repeat proteoglycans, fibromodulin and chondroadherin

The small leucine-rich proteoglycans (SLRPs) are important regulators of extracellular matrix assembly and cell signalling. We have determined crystal structures at similar to 2.2 angstrom 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 alpha 2 beta 1 maps to an alpha-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 (0 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. (C) 2017 The Authors. Published by Elsevier B.V.