ArticleProceedings of the National Academy of Sciences of the United States of America2011
Binding of alpha-thrombin to surface-anchored platelet glycoprotein Ib(alpha) sulfotyrosines through a two-site mechanism involving exosite I.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.Scientific reports · 2021Trial
- Platelet-Collagen Interactions in Hemostatic Mechanisms.Advanced healthcare materials · 2026Review
- Detection of α-Thrombin with Platelet Glycoprotein Ibα (GP1bα) for the Development of a Coagulation Marker.ACS omega · 2024Article
- Sequence features, structure, ligand interaction, and diseases in small leucine rich repeat proteoglycans.Journal of cell communication and signaling · 2021Review
- Review
- Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.Journal of thrombosis and haemostasis : JTH · 2021Article
- Platelet Membrane Receptor Proteolysis: Implications for Platelet Function.Frontiers in cardiovascular medicine · 2020Review
- Platelet-type von Willebrand disease: Local disorder of the platelet GPIbα β-switch drives high-affinity binding to von Willebrand factor.Journal of thrombosis and haemostasis : JTH · 2019Article
- Humanized GPIbα-von Willebrand factor interaction in the mouse.Blood advances · 2018Article
- Review
- New Concepts and Mechanisms of Platelet Activation Signaling.Physiology (Bethesda, Md.) · 2017Review
- Article
- Article
- Genetic deletion of platelet glycoprotein Ib alpha but not its extracellular domain protects from atherosclerosis.Thrombosis and haemostasis · 2014Article
- Substantial non-electrostatic forces are needed to induce allosteric disruption of thrombin's active site through exosite 2.Biochemical and biophysical research communications · 2014Article
- Review
- Structural and energetic determinants of tyrosylprotein sulfotransferase sulfation specificity.Bioinformatics (Oxford, England) · 2014Article
- Structural basis of regulation of von Willebrand factor binding to glycoprotein Ib.The Journal of biological chemistry · 2014Article
- GpIbα interacts exclusively with exosite II of thrombin.Journal of molecular biology · 2014Article
- Echicetin coated polystyrene beads: a novel tool to investigate GPIb-specific platelet activation and aggregation.PloS one · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The involvement of exosite I in α-thrombin (FIIa) binding to platelet glycoprotein Ibα (GPIbα), which could influence interactions with other substrates, remains undefined. To address the problem, we generated the GPIbα amino terminal domain (GPIbα-N) fully sulfated on three tyrosine residues and solved the structure of its complex with FIIa. We found that sulfotyrosine (Tys) 278 enhances the interaction mainly by establishing contacts with exosite I. We then evaluated how substituting tyrosine with phenylalanine, which cannot be sulfated, affects FIIa binding to soluble or surface-immobilized GPIbα-N. Mutating Tyr(276), which mostly contacts exosite II residues, markedly reduced FIIa interaction with both soluble and immobilized GPIbα-N; mutating Tyr(278) or Tyr(279), which mostly contact exosite I residues, reduced FIIa complexing in solution by 0-20% but affinity for immobilized GPIbα-N 2 to 6-fold, respectively. Moreover, three exosite I ligands--aptamer HD1, hirugen, and lepirudin--did not interfere with soluble FIIa complexing to GPIbα-N, excluding that their binding caused allosteric effects influencing the interaction; nonetheless, all impaired FIIa binding to immobilized GPIbα-N and platelet GPIb nearly as much as aptamer HD22 and heparin, both exosite II ligands. Bound HD1 and hirugen alter Trp(148) orientation in a loop near exosite I preventing contacts with the sulfate oxygen atoms of Tys(279). These results support a mechanism in which binding occurs when the two exosites of one FIIa molecule independently interact with two immobilized GPIbα molecules. Through exosite engagement, GPIbα may influence FIIa-dependent processes relevant to hemostasis and thrombosis.
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