title: Crystal structure of α5β1 integrin ectodomain: atomic details of the fibronectin receptor.
abstract: Integrin α5β1 is a major cellular receptor for the extracellular matrix protein fibronectin and plays a fundamental role during mammalian development. A crystal structure of the α5β1 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 β1 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 α5β1 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.
authors.affiliation: Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nagae
authors.forename: Suyong
authors.initials: S
authors.lastname: Re
authors.forename: Emiko
authors.initials: E
authors.lastname: Mihara
authors.forename: Terukazu
authors.initials: T
authors.lastname: Nogi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
authors.forename: Junichi
authors.initials: J
authors.lastname: Takagi
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D039081:Integrin alpha5beta1; D011994:Recombinant Proteins