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Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation.

John J Dumas·Ravindra Kumar·Jasbir Seehra·William S Somers·Lidia Mosyak
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Abstract

Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbalpha-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbalpha with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbalpha-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.

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Binding SitesBlood PlateletsCrystallizationCrystallography, X-RayHumansHydrogen BondingHydrophobic and Hydrophilic InteractionsModels, MolecularPlatelet AdhesivenessPlatelet AggregationPlatelet Glycoprotein GPIb-IX ComplexProtein BindingProtein ConformationProtein Structure, SecondaryProtein Structure, TertiaryThrombinJournal Article

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John J Dumas, Ravindra Kumar, Jasbir Seehra, William S Somers, Lidia Mosyak. 2003-07-11. Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation.. https://doi.org/10.1126/science.1083917

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