2gi7
From Proteopedia
Crystal structure of human platelet Glycoprotein VI (GPVI)
Structural highlights
DiseaseGPVI_HUMAN Bleeding diathesis due to glycoprotein VI deficiency. The disease is caused by mutations affecting the gene represented in this entry. FunctionGPVI_HUMAN Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely FYN or LYN) and SYK, the adapter protein LAT and leads to the activation of PLCG2.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedActivation 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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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