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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.
 Previous Article | Next Article 
Submitted January 29, 2006
Accepted March 23, 2006
Structural basis for platelet collagen responses by the
immune-type receptor glycoprotein VI
Katsunori Horii, Mark L Kahn, and Andrew B Herr*
Department of Molecular Genetics, Biochemistry & Microbiology, University of Cincinnati
Department of Medicine, Division of Cardiology, University of Pennsylvania, Philadelphia, PA
* Corresponding author; email: andrew.herr{at}uc.edu.
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 two 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 two 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.
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