4mmz
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Integrin AlphaVBeta3 ectodomain bound to an antagonistic tenth domain of Fibronectin== | |
| + | <StructureSection load='4mmz' size='340' side='right'caption='[[4mmz]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4mmz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MMZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mmz OCA], [https://pdbe.org/4mmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mmz RCSB], [https://www.ebi.ac.uk/pdbsum/4mmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mmz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ITAV_HUMAN ITAV_HUMAN] The alpha-V integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Integrins are important therapeutic targets. However, current RGD-based anti-integrin drugs are also partial agonists, inducing conformational changes that trigger potentially fatal immune reactions and paradoxical cell adhesion. Here we describe the first crystal structure of alphaVbeta3 bound to a physiologic ligand, the tenth type III RGD domain of wild-type fibronectin (wtFN10), or to a high-affinity mutant (hFN10) shown here to act as a pure antagonist. Comparison of these structures revealed a central pi-pi interaction between Trp1496 in the RGD-containing loop of hFN10 and Tyr122 of the beta3 subunit that blocked conformational changes triggered by wtFN10 and trapped hFN10-bound alphaVbeta3 in an inactive conformation. Removing the Trp1496 or Tyr122 side chains or reorienting Trp1496 away from Tyr122 converted hFN10 into a partial agonist. These findings offer new insights into the mechanism of integrin activation and a basis for the design of RGD-based pure antagonists. | ||
| - | + | Structural basis for pure antagonism of integrin alphaVbeta3 by a high-affinity form of fibronectin.,Van Agthoven JF, Xiong JP, Alonso JL, Rui X, Adair BD, Goodman SL, Arnaout MA Nat Struct Mol Biol. 2014 Apr;21(4):383-8. doi: 10.1038/nsmb.2797. Epub 2014 Mar , 23. PMID:24658351<ref>PMID:24658351</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4mmz" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Fibronectin 3D structures|Fibronectin 3D structures]] | ||
| + | *[[Integrin 3D structures|Integrin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Arnaout MA]] | ||
| + | [[Category: Xiong J]] | ||
| + | [[Category: Van Agthoven J]] | ||
Current revision
Integrin AlphaVBeta3 ectodomain bound to an antagonistic tenth domain of Fibronectin
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