Crystal Structure of the Extracellular Segment of Integrin αVβ3

TLDR

Integrins are αβ heterodimeric receptors that mediate divalent cation‑dependent cell‑cell and cell‑matrix adhesion through tightly regulated ligand interactions. The crystal structure of the extracellular portion of integrin αVβ3 at 3.1 Å resolution reveals a bent, ovoid head–tail architecture with a β‑propeller/A‑domain interface resembling Gα/Gβ, a MIDAS site poised for ligand binding adjacent to a calcium‑binding regulatory site.

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 inter-subunit 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/Gβ interface 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.