Title : Crystal structure of α5 β 1 integrin ectodomain : atomic details of the fibronectin receptor
Abstract :
Integrin α5 β 1 is a major cellular receptor for the extracellular matrix protein fibronectin and plays a fundamental role during mammalian development
A crystal structure of the α5 β 1 integrin headpiece fragment bound by an allosteric inhibitory antibody was determined at a 2.9-Å resolution both in the absence and presence of a ligand peptide containing the Arg-Gly-Asp (RGD) sequence
The antibody-bound β 1 chain accommodated the RGD ligand with very limited structural changes, which may represent the initial step of cell adhesion mediated by nonactivated integrins
Furthermore, a molecular dynamics simulation pointed to an important role for Ca(2 +) in the conformational coupling between the ligand-binding site and the rest of the molecule
The RGD-binding pocket is situated at the center of a trenchlike exposed surface on the top face of α5 β 1 devoid of glycosylation sites
The structure also enabled the precise prediction of the acceptor residue for the auxiliary synergy site of fibronectin on the α5 subunit , which was experimentally confirmed by mutagenesis and kinetic binding assays