2gi7
From Proteopedia
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'''Crystal structure of human platelet Glycoprotein VI (GPVI)''' | '''Crystal structure of human platelet Glycoprotein VI (GPVI)''' | ||
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[[Category: Horii, K.]] | [[Category: Horii, K.]] | ||
[[Category: Kahn, M L.]] | [[Category: Kahn, M L.]] | ||
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Revision as of 02:08, 4 May 2008
Crystal structure of human platelet Glycoprotein VI (GPVI)
Overview
Activation of circulating platelets by exposed vessel wall collagen is a primary step in the pathogenesis of heart attack and stroke, and drugs to block platelet activation have successfully reduced cardiovascular morbidity and mortality. In humans and mice, collagen activation of platelets is mediated by glycoprotein VI (GPVI), a receptor that is homologous to immune receptors but bears little sequence similarity to known matrix protein adhesion receptors. Here we present the crystal structure of the collagen-binding domain of human GPVI and characterize its interaction with a collagen-related peptide. Like related immune receptors, GPVI contains 2 immunoglobulin-like domains arranged in a perpendicular orientation. Significantly, GPVI forms a back-to-back dimer in the crystal, an arrangement that could explain data previously obtained from cell-surface GPVI inhibition studies. Docking algorithms identify 2 parallel grooves on the GPVI dimer surface as collagen-binding sites, and the orientation and spacing of these grooves precisely match the dimensions of an intact collagen fiber. These findings provide a structural basis for the ability of an immune-type receptor to generate signaling responses to collagen and for the development of GPVI inhibitors as new therapies for human cardiovascular disease.
About this Structure
2GI7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI., Horii K, Kahn ML, Herr AB, Blood. 2006 Aug 1;108(3):936-42. PMID:16861347 Page seeded by OCA on Sun May 4 05:08:09 2008
