Crystal structure of the extracellular segment of integrin alpha V beta 3

Integrins are alpha beta heterodimeric receptors that mediate divalent cati on-dependent cell-cell and cell-matrix adhesion through tightly regulated i nteractions with ligands. We have solved the crystal structure of the extra cellular portion of integrin alphaV beta3 at 3.1 Angstrom resolution. Its 1 2 domains assemble into an ovoid "head" and two "tails." In the crystal, al phaV beta3 is severely bent at a defined region in its tails, reflecting an unusual flexibility that may be linked to integrin regulation. The main in tersubunit interface ties within the head, between a seven-bladed beta -pro peller from alphaV and an A domain from beta3, and bears a striking resembl ance to the G alpha /G beta interface in G proteins. A metal ion-dependent adhesion site (MIDAS) in the betaA domain is positioned to participate in a ligand-binding interface formed of loops from the propeller and betaA doma ins. MIDAS ties adjacent to a calcium-binding site with a potential regulat ory function.