Crystal Structure of the GpIbα-Thrombin Complex Essential for Platelet Aggregation
- 11 July 2003
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 301 (5630) , 222-226
- https://doi.org/10.1126/science.1083917
Abstract
Direct interaction between platelet receptor glycoprotein Ibα (GpIbα) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbα-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbα-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbα with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbα-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbα-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.Keywords
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