Structures of glycoprotein Ib[alpha] and its complex with von Willebrand factor A1 domain

Transient interactions of platelet-receptor glycoprotein Ib[alpha] (GpIb[alpha]) and the plasma protein von Willebrand factor (VWF) reduce platelet velocity at sites of vascular damage and play a role in haemostasis and thrombosis. Here we present structures of the GpIb[alpha] amino-terminal domain...

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Published inScience (American Association for the Advancement of Science) Vol. 297; no. 5584; p. 1176
Main Authors Huizinga, Eric G, Tsuji, Shizuko, Romijn, Roland A.P, Schiphorst, Marion E, de Groot, Philip G, Sixma, Jan J, Gros, Piet
Format Journal Article
LanguageEnglish
Published American Association for the Advancement of Science 16.08.2002
Subjects
Blood platelets
Glycoproteins
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Summary:Transient interactions of platelet-receptor glycoprotein Ib[alpha] (GpIb[alpha]) and the plasma protein von Willebrand factor (VWF) reduce platelet velocity at sites of vascular damage and play a role in haemostasis and thrombosis. Here we present structures of the GpIb[alpha] amino-terminal domain and its complex with the VWF domain A1. In the complex, GpIb[alpha] wraps around one side of A1, providing two contact areas bridged by an area of solvated charge interaction. The structures explain the effects of gain-of-function mutations related to bleeding disorders and provide a model for shear-induced activation. These detailed insights into the initial interactions in platelet adhesion are relevant to the development of antithrombotic drugs.
ISSN:0036-8075