title: Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family.
abstract: Cartilage oligomeric matrix protein (COMP) and type IX collagen are key structural components of the cartilage extracellular matrix and have important roles in tissue development and homeostasis. Mutations in the genes encoding these glycoproteins result in two related human bone dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia, which together comprise a "bone dysplasia family." It has been proposed that these diseases have a similar pathophysiology, which is highlighted by the fact that mutations in either the COMP or the type IX collagen genes produce multiple epiphyseal dysplasia, suggesting that their gene products interact. To investigate the interactions between COMP and type IX collagen, we have used rotary shadowing electron microscopy and real time biomolecular (BIAcore) analysis. Analysis of COMP-type IX collagen complexes demonstrated that COMP interacts with type IX collagen through the noncollagenous domains of type IX collagen and the C-terminal domain of COMP. Furthermore, peptide mapping identified a putative collagen-binding site that is associated with known human mutations. These data provide evidence that disruptions to COMP-type IX collagen interactions define a pathogenetic mechanism in a bone dysplasia family.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road., Manchester M13 9PT, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Holden
authors.forename: R S
authors.initials: RS
authors.lastname: Meadows
authors.forename: K L
authors.initials: KL
authors.lastname: Chapman
authors.forename: M E
authors.initials: ME
authors.lastname: Grant
authors.forename: K E
authors.initials: KE
authors.lastname: Kadler
authors.forename: M D
authors.initials: MD
authors.lastname: Briggs
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001848:Bone Diseases, Developmental / Q000209:etiology*; D002356:Cartilage / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000648:ultrastructure; D006023:Glycoproteins / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D064235:Matrilin Proteins; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010449:Peptide Mapping; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C577553:TSP5 protein, human; D003094:Collagen