title: Crystal structure of the extracellular segment of integrin alpha Vbeta3 in complex with an Arg-Gly-Asp ligand.
abstract: The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3.
authors.affiliation: Renal Unit, Leukocyte Biology and Inflammation Program, Structural Biology Program, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Xiong
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.forename: Matthias
authors.initials: M
authors.lastname: Frech
authors.forename: Simon L
authors.initials: SL
authors.lastname: Goodman
authors.forename: M Amin
authors.initials: MA
authors.lastname: Arnaout
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008024:Ligands; D008345:Manganese / Q000737:chemistry; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D019030:Receptors, Vitronectin / Q000737:chemistry* / Q000378:metabolism*; D012910:Snake Venoms
chemical_list: D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019030:Receptors, Vitronectin; D012910:Snake Venoms; D008345:Manganese; C422910:Cilengitide; C047981:arginyl-glycyl-aspartic acid