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Blood, 1 August 2006, Vol. 108, No. 3, pp. 936-942. Prepublished online as a Blood First Edition Paper on April 6, 2006; DOI 10.1182/blood-2006-01-010215. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-01-010215v1 108/3/936    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Horii, K. Articles by Herr, A. B. Search for Related Content PubMed PubMed Citation Articles by Horii, K. Articles by Herr, A. B. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI Katsunori Horii, Mark L. Kahn, and Andrew B. Herr From the Department of Molecular Genetics, Biochemistry & Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH; and the Department of Medicine, Division of Cardiology, University of Pennsylvania, Philadelphia, PA. 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 immunetype receptor to generate signaling responses to collagen and for the development of GPVI inhibitors as new therapies for human cardiovascular disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Dumont, D. Lasne, C. Rothschild, M. Bouabdelli, V. Ollivier, C. Oudin, N. Ajzenberg, B. Grandchamp, and M. Jandrot-Perrus Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations Blood, August 27, 2009; 114(9): 1900 - 1903. [Abstract] [Full Text] [PDF] A. B. Herr and R. W. Farndale Structural Insights into the Interactions between Platelet Receptors and Fibrillar Collagen J. Biol. Chem., July 24, 2009; 284(30): 19781 - 19785. [Abstract] [Full Text] [PDF] X. Tang, S. Narayanan, G. Peruzzi, A. Apara, K. Natarajan, D. H. Margulies, J. E. Coligan, and F. 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Davies, L. Joutsi-Korhonen, D. J. Onley, A. B. Herr, R. W. Farndale, and W. H. Ouwehand Selective Blockade of Glycoprotein VI Clustering on Collagen Helices J. Biol. Chem., November 3, 2006; 281(44): 33505 - 33510. [Abstract] [Full Text] [PDF]

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