Crystal structure of the extracellular segment of integrin αVβ3

Integrins are alpha beta heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands. We have solved the crystal structure of the extracellular portion of integrin alphaV beta3 at 3.1 Angstrom resolution. Its 12 domains assemble into an ovoid head and two tails. In the crystal, alphaV beta3 is severely bent at a defined region in its tails, reflecting an unusual flexibility that may be linked to integrin regulation. The main intersubunit interface ties within the head, between a seven-bladed beta -propeller from alphaV and an A domain from beta3, and bears a striking resemblance 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 domains. MIDAS ties adjacent to a calcium-binding site with a potential regulatory function.