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PDBsum entry 3fby
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Cell adhesion
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PDB id
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3fby
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References listed in PDB file
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Key reference
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Title
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The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, Glycosaminoglycan and integrin binding.
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Authors
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K.Tan,
M.Duquette,
A.Joachimiak,
J.Lawler.
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Ref.
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Faseb J, 2009,
23,
2490-2501.
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PubMed id
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Abstract
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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.
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