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PDBsum entry 1k15
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Blood clotting
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PDB id
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1k15
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References listed in PDB file
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Key reference
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Title
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Molecular modeling of the seven tandem leucine-Rich repeats within the ligand-Binding region of platelet glycoprotein ib alpha.
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Authors
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J.C.Whisstock,
Y.Shen,
J.A.López,
R.K.Andrews,
M.C.Berndt.
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Ref.
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Thromb Haemost, 2002,
87,
329-333.
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PubMed id
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Abstract
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Platelet glycoprotein (GP)Ib-IX-V mediates von Willebrand Factor (vWF)-dependent
adhesion to vascular subendothelium at high shear in (patho)physiological
thrombus formation. The ligand-binding domain of GPIb-IX-V is within the
N-terminal 282 residues of GPIb alpha, that contains seven tandem leucine-rich
repeats (Leu36-Ala200). Repeats 2-4 are critical for vWF binding. In this study,
we have built molecular models of the seven leucine-rich repeats of human,
canine and mouse GPIb alpha, providing novel insights into the species-specific
interaction between human vWF and its receptor. Interestingly, a major
difference between the models was a large negatively charged patch on the
concave face of human, but not canine, repeats 2-4. In addition, five individual
mutations within the leucine-rich repeats of GPIb alpha associated with the
bleeding disorder Bernard-Soulier syndrome, that result in dysfunctional vWF
binding, were mapped to the model of human GPIb alpha. This provides the basis
for relating these genetic lesions to abnormal function of the receptor.
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