Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Ibalpha
Thrombin bound to platelets contributes to stop bleeding and, in pathological conditions, may cause vascular thrombosis. We have determined the structure of platelet glycoprotein Ibalpha (GpIbalpha) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIbalpha that bind to exosite...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2003-07, Vol.301 (5630), p.218-221 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Celikel, Reha McClintock, Richard A Roberts, James R Mendolicchio, G Loredana Ware, Jerry Varughese, Kottayil I Ruggeri, Zaverio M |
| description | Thrombin bound to platelets contributes to stop bleeding and, in pathological conditions, may cause vascular thrombosis. We have determined the structure of platelet glycoprotein Ibalpha (GpIbalpha) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIbalpha that bind to exosite II and exosite I of two distinct alpha-thrombin molecules, respectively. GpIbalpha occupancy may be sequential, as the site binding to alpha-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 alpha-thrombin function by mediating GpIbalpha clustering and cleavage of protease-activated receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I. |
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We have determined the structure of platelet glycoprotein Ibalpha (GpIbalpha) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIbalpha that bind to exosite II and exosite I of two distinct alpha-thrombin molecules, respectively. GpIbalpha occupancy may be sequential, as the site binding to alpha-thrombin exosite I appears to be cryptic in the unoccupied receptor but exposed when a first thrombin molecule is bound through exosite II. 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We have determined the structure of platelet glycoprotein Ibalpha (GpIbalpha) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIbalpha that bind to exosite II and exosite I of two distinct alpha-thrombin molecules, respectively. GpIbalpha occupancy may be sequential, as the site binding to alpha-thrombin exosite I appears to be cryptic in the unoccupied receptor but exposed when a first thrombin molecule is bound through exosite II. 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| ispartof | Science (American Association for the Advancement of Science), 2003-07, Vol.301 (5630), p.218-221 |
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| language | eng |
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| source | MEDLINE; American Association for the Advancement of Science; Jstor Complete Legacy |
| subjects | Binding Sites Blood Coagulation Blood Platelets - chemistry Blood Platelets - metabolism Crystallization Crystallography, X-Ray Fibrinogen - metabolism Humans Hydrogen Bonding Ligands Models, Molecular Mutation Platelet Aggregation Platelet Glycoprotein GPIb-IX Complex - chemistry Platelet Glycoprotein GPIb-IX Complex - genetics Platelet Glycoprotein GPIb-IX Complex - metabolism Protein Binding Protein Conformation Protein Structure, Tertiary Recombinant Proteins - chemistry Recombinant Proteins - metabolism Thrombin - chemistry Thrombin - metabolism |
| title | Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Ibalpha |
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