Crystal structure of the extracettutar segment of integrin αVβ3

Abstract

Integrins are αβ 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 αVβ3 at 3.1 Å resolution. Its 12 domains assemble into an ovoid "head" and two "tails." In the crystal, αVβ3 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 lies within the head, between a seven-bladed β-propeller from αV and an A domain from β3, and bears a striking resemblance to the Gα/Gβinterface in G proteins. A metal ion-dependent adhesion site (MIDAS) in the βA domain is positioned to participate in a ligand-binding interface formed of loops from the propeller and βA domains. MIDAS lies adjacent to a calcium-binding site with a potential regulatory function.