3vi4

Crystal structure of alpha5beta1 integrin headpiece in complex with RGD peptide

spinqualitylabelsall models 3vi4, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3vi4 is a 10 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, CA, MG, NAG, MAN Gene: FNRA, ITGA5 (HUMAN), FNRB, ITGB1, MDF2, MSK12 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ITA5_HUMAN] Integrin alpha-5/beta-1 is a receptor for fibronectin and fibrinogen. It recognizes the sequence R-G-D in its ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. [ITB1_HUMAN] Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. Isoform beta-1B interferes with isoform beta-1A resulting in a dominant negative effect on cell adhesion and migration (in vitro). In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. When associated with alpha-7/beta-1 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and GNB2L1/RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin Molecular Playground/IntegrinBeta1

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