Recombinant Human Integrin alpha 2b beta 3 Protein, CF

Integrin alpha2b beta3 (also alphaIIb beta3 or GPIIbIIIa) is the only alpha2b integrin and shares the beta3 subunit only with alphaV beta3 (1‑3). It is the non‑covalent heterodimer of type I transmembrane subunits, alpha2b/CD41 (present as a disulfide‑linked complex of 114 kDa heavy and 22 kDa light chains) and 93 kDa beta3/CD61 (1‑3). It is the most abundant integrin expressed by megakaryocytes and platelets, both on the surface and within alpha granules (1, 2). Deficiencies of alpha2b beta3 produce Glanzmann thrombasthenia, a potentially serious bleeding disorder (4). In its constitutively inactive state, alpha2b beta3 is flexed within the extracellular domains. Activation, either by intracellular signaling or by Mg²⁺ or Mn²⁺ binding, extends the integrin to expose the ligand binding site created by interaction of the beta3 vWFA domain with the alpha2b  beta-propeller structure (1). The 962 aa human alpha2b ECD shares 78‑83% aa sequence identity with mouse, rat, canine, equine and porcine  alpha2b while the 685 aa human  beta3 ECD shares 95% aa identity with horse and dog, and 89‑92% aa identity with mouse, rat and porcine beta3. It is unclear whether splice variants of beta3 that differ in the cytoplasmic domain are expressed significantly in platelets (5‑7). However, platelet expression of a beta3 splice variant that produces a soluble 60 kDa beta3 isoform, and an alpha2b isoform lacking aa 948‑982, have been reported (7, 8). Active cell surface alpha2b beta3 adheres to fibrinogen, mediating platelet/platelet interactions that initiate a cascade of platelet activation and aggregation, extracellular matrix adhesion, formation of thrombi and clot retraction (1). It also binds matrix proteins that have an RGD motif, including fibronectin, plasminogen, prothrombin, thrombospondin and vitronectin (1, 2). Targeting of alpha2b beta3 by therapeutic antibodies or small molecules can inhibit formation of thrombi in patients with acute coronary syndrome, and potentially inhibits tumor angiogenesis and metastasis by blocking interaction of platelet alpha2b beta3 with tumor cells (1, 9).