Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Ib(alpha)

Thrombin bound to platelets contributes to stop bleeding and, in pathological conditions, may cause vascular thrombosis. We have determined the structure of platelet glycoprotein Ib (GpIb) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIb that bind to exosite II and exosite...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2003-07, Vol.301 (5630), p.218-221
Main Authors: Celikel, Reha, McClintock, Richard A, Roberts, James R, G Loredana Mendolicchio
Format: Article
Language:English
Subjects:
Neurotransmitters
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Summary:Thrombin bound to platelets contributes to stop bleeding and, in pathological conditions, may cause vascular thrombosis. We have determined the structure of platelet glycoprotein Ib (GpIb) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIb that bind to exosite II and exosite I of two distinct -thrombin molecules, respectively. GpIb occupancy may be sequential, as the site binding to -thrombin exosite I appears to be cryptic in the unoccupied receptor but exposed when a first thrombin molecule is bound through exosite II. These interactions may modulate -thrombin function by mediating GpIb clustering and cleavage of protease-activated receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I.
ISSN:0036-8075
1095-9203