Integrin alpha-IIb beta-3 (αIIbβ3 (also GPIIb/IIIa))

Integrin alpha-IIb beta-3 (αIIbβ3, Glycoprotein IIb/IIIa) is a highly abundant, heterodimeric integrin receptor complex exclusively and densely expressed on platelets and megakaryocytes[2][4][7][8]. It is essential for platelet aggregation, acting as the principal receptor for fibrinogen, fibronectin, von Willebrand factor, and other extracellular matrix ligands containing an RGD motif[1][2][6][8]. Upon platelet activation, αIIbβ3 undergoes a conformational change, increasing its affinity for ligands, leading to cross-linking of platelets and thrombus formation[3][4][7]. The receptor is central to hemostasis and thrombosis, and its deficiency results in Glanzmann thrombasthenia, a rare bleeding disorder[2]. αIIbβ3 is a validated therapeutic target: clinically used antagonists (abciximab, eptifibatide, tirofiban) inhibit its function to prevent thrombotic complications in acute coronary syndromes and during percutaneous coronary interventions, though safety concerns, notably bleeding and thrombocytopenia, limit duration and indications[5][7][8]. Its major roles are restricted to platelets, but it is also occasionally expressed on tumor cells and other hematopoietic cells[5]. The structure consists of noncovalently linked αIIb and β3 subunits, each spanning the membrane once and containing extensive extracellular ligand-binding regions and short cytoplasmic domains mediating bidirectional signaling and cytoskeletal interactions[1][4][7]. Caveats: The target is sometimes also called "integrin alpha 2b beta 3" but "integrin alpha-IIb beta-3" or "Glycoprotein IIb/IIIa" are considered the canonical forms[2][8].

Other names

Glycoprotein IIb/IIIaGPIIb/IIIaIntegrin αIIbβ3CD41/CD61 complex

Competitive antagonism at the RGD (arginine-glycine-aspartate) ligand binding site, inhibiting fibrinogen/von Willebrand factor binding. Inhibition of platelet aggregation and thrombus formation. Blocking outside-in and inside-out signaling in platelets.