Human Integrin  alphaV beta3 Antibody

Integrin alphaV beta3 together with alphaIIb beta₃, constitutes the only known beta3 Integrins (1‑3). The non-covalent heterodimer of 170 kDa alphaV/CD51 and 93 kDa beta₃/CD61 subunits shows wide expression, notably by endothelial cells and osteoclasts (2‑4). Each subunit has a transmembrane sequence and a short cytoplasmic tail connected to the cytoskeleton. Active cell surface alphaV beta3 adheres to matrix proteins including vitronectin, fibronectin, fibrinogen and thrombospondin (2, 3). The ligand binding site of alphaV beta3 is in the N-terminal head region, formed by interaction of the beta3 vWFA domain with the alphaV beta-propeller structure (4). The alphaV subunit contributes a thigh and a calf region, while the beta3 subunit contains a PSI domain and four cysteine-rich I-EGF folds. The alphaV subunit domains termed thigh, calf-1 and calf-2 generate a “knee” region that is bent when the alphaV beta3 is in its constitutively inactive state. Activation, either by “inside out” signaling or by Mg²⁺ or Mn²⁺ binding, extends the Integrin to expose its ligand binding site (1, 4). Two splice variants of beta3 (b and c) diverge over the last 21 amino acids (aa) and lack cytoplasmic phosphorylation sites (5, 6). Another beta3 splice variant diverges after the vWFA domain, producing a soluble 60 kDa form in platelets and endothelial cells (7). alphaV beta3 is essential for the maturation of osteoclasts and their binding and resorption of bone; it also, however, promotes their apoptosis (8, 9). M-CSF R and alphaV beta3 share signaling pathways during osteoclastogenesis, and deletion of either molecule causes osteopetrosis (8, 9). Also cell entry of several viruses is mediated by alphaV beta3 (4, 10). The 962 aa human alphaV ECD (11) shares 92‑95% aa sequence identity with mouse, rat and cow  alphaV while the 685 aa human beta₃ ECD (12) shares 95% aa identity with horse and dog, and 89‑92% aa identity with mouse, rat and pig beta₃.