Department of Life Sciences, Imperial College London, London, United Kingdom.
Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
Matrix Biol. 2017 Nov;63:106-116. doi: 10.1016/j.matbio.2017.02.002. Epub 2017 Feb 17.
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.
小富含亮氨酸的蛋白聚糖 (SLRPs) 是细胞外基质组装和细胞信号传导的重要调节剂。我们已经确定了人类纤调蛋白和软骨粘连蛋白的晶体结构，它们是两种与胶原蛋白结合的 SLRPs，分辨率约为 2.2Å。它们的整体折叠与典型的 SLRP decorin 相似，但纤调蛋白和软骨粘连蛋白都不像 decorin 那样形成稳定的二聚体。先前鉴定的整合素 α2β1 结合位点位于软骨粘连蛋白 C 末端帽区的α-螺旋上。对胶原工具包的研究揭示了软骨粘连蛋白在 II 型胶原中的独特结合位点，而与 III 型胶原没有结合。含有 GAOGPSGFQGLOGPOGPO（O 是羟脯氨酸）序列的三螺旋肽在溶液中与软骨粘连蛋白形成稳定的复合物。在原纤维状的 I 型和 II 型胶原中，该序列与胶原交联位点 KGHR 对齐，提示软骨粘连蛋白在交联中的作用。
