3vi4

Publication Abstract from PubMed

Integrin alpha5beta1 is a major cellular receptor for the extracellular matrix protein fibronectin and plays a fundamental role during mammalian development. A crystal structure of the alpha5beta1 integrin headpiece fragment bound by an allosteric inhibitory antibody was determined at a 2.9-A resolution both in the absence and presence of a ligand peptide containing the Arg-Gly-Asp (RGD) sequence. The antibody-bound beta1 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 alpha5beta1 devoid of glycosylation sites. The structure also enabled the precise prediction of the acceptor residue for the auxiliary synergy site of fibronectin on the alpha5 subunit, which was experimentally confirmed by mutagenesis and kinetic binding assays.

Crystal structure of alpha5beta1 integrin ectodomain: Atomic details of the fibronectin receptor.,Nagae M, Re S, Mihara E, Nogi T, Sugita Y, Takagi J J Cell Biol. 2012 Apr 2;197(1):131-40. Epub 2012 Mar 26. PMID:22451694^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.