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Platelets in Thrombotic and Non-Thrombotic Disorders pp 99–112Cite as

αIIbβ3 (GPIIb/IIIa) Structure and Function

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Abstract

The platelet membrane protein αIIbβ3, otherwise known as glycoprotein IIb/IIIa (GPIIb/IIIa), is a member of the ubiquitous integrin family of transmembrane (TM) heterodimers and is absolutely required for platelet aggregation. αIIbβ3 mediates platelet aggregation when fibrinogen or von Willebrand factor (vWF) bound to active αIIbβ3 cross-links adjacent stimulated platelets into stable aggregates. αIIbβ3 heterodimers are assembled from αIIb and β3 monomers in the endoplasmic reticulum. Mutations impairing the synthesis of either subunit decrease αIIbβ3 expression, thereby causing the autosomal bleeding disorder Glanzmann thrombasthenia. Conversely, αIIbβ3-mediated platelet aggregation is responsible for the arterial thrombi that cause heart attack and stroke. αIIbβ3 is present on platelets in an equilibrium between an inactive bent conformation and an active extended conformation. To prevent spontaneous platelet aggregation, however, αIIbβ3 on circulating platelets is constrained to its inactive conformation via intramolecular interactions involving its transmembrane and cytoplasmic domains. When platelets encounter a damaged blood vessel, stimulation by agonists such as thrombin and ADP causes nearly instantaneous αIIbβ3 activation by inducing talin-1 and kindlin-3 binding to the β3 cytoplasmic domain, thereby relieving the transmembrane and cytoplasmic domain restraints. αIIbβ3 binds to fibrin as well as fibrinogen. Thus, following αIIbβ3 activation, αIIbβ3 bound to fibrin transmits the retraction forces that consolidate fibrin clots, enabling them to resist the potentially disruptive shear forces present in circulating blood.

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Authors and Affiliations

  1. Hematology-Oncology Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 814 BRB II/III, 421 Curie Blvd., Philadelphia, PA, 19104, USA

    Joel S. Bennett M.D.

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  1. Joel S. Bennett M.D.
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Correspondence to Joel S. Bennett M.D. .

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Editors and Affiliations

  1. Department of Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia , Perugia, Italy

    Paolo Gresele

  2. Houston Methodist Hospital , Houston, Texas, USA

    Neal S. Kleiman

  3. Bloodworks Northwest, University of Washington , Seattle, Washington, USA

    José A. Lopez

  4. Sackler Inst of Pulmonary Pharmacol, King’s College London, London, United Kingdom

    Clive P. Page

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Bennett, J.S. (2017). αIIbβ3 (GPIIb/IIIa) Structure and Function. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_8

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