Title : The crystal structure of the signature
domain of
cartilage oligomeric matrix protein : implications for
collagen, glycosaminoglycan and integrin binding
Abstract :
- Cartilage oligomeric matrix protein ( COMP ), or thrombospondin-5 ( TSP-5), is a secreted glycoprotein that is important for growth plate organization and function
- Mutations in COMP cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1)
- In this study, we determined the structure of a recombinant protein that contains the last epidermal growth factor repeat, the type 3 repeats and the C-terminal domain (CTD) of COMP to 3.15-A resolution limit by X-ray crystallography
- The CTD is a beta-sandwich that is composed of 15 antiparallel beta-strands, and the type 3 repeats are a contiguous series of calcium binding sites that associate with the CTD at multiple points
- The crystal packing reveals an exposed potential metal-ion-dependent adhesion site ( MIDAS ) on one edge of the beta-sandwich that is common to all TSPs and may serve as a binding site for collagens and other ligands
- Disease-causing mutations in COMP disrupt calcium binding, disulfide bond formation, intramolecular interactions, or sites for potential ligand binding
- The structure presented here and its unique molecular packing in the crystal identify potential interactive sites for glycosaminoglycans , integrins, and collagens, which are key to cartilage structure and function