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4o02
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==AlphaVBeta3 integrin in complex with monoclonal antibody FAB fragment.== | |
| + | <StructureSection load='4o02' size='340' side='right'caption='[[4o02]], [[Resolution|resolution]] 3.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4o02]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O02 FirstGlance]. <br> | ||
| + | </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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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=4o02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o02 OCA], [https://pdbe.org/4o02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o02 RCSB], [https://www.ebi.ac.uk/pdbsum/4o02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o02 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 == | ||
| + | The function-blocking, non-RGD-containing, and primate-specific mouse monoclonal antibody 17E6 binds the alphaV subfamily of integrins. 17E6 is currently in phase II clinical trials for treating cancer. To elucidate the structural basis of recognition and the molecular mechanism of inhibition, we crystallized alphaVbeta3 ectodomain in complex with the Fab fragment of 17E6. Protein crystals grew in presence of the activating cation Mn(2+). The integrin in the complex and in solution assumed the genuflected conformation. 17E6 Fab bound exclusively to the Propeller domain of the alphaV subunit. At the core of alphaV-Fab interface were interactions involving Propeller residues Lys-203 and Gln-145, with the latter accounting for primate specificity. The Propeller residue Asp-150, which normally coordinates Arg of the ligand Arg-Gly-Asp motif, formed contacts with Arg-54 of the Fab that were expected to reduce soluble FN10 binding to cellular alphaVbeta3 complexed with 17E6. This was confirmed in direct binding studies, suggesting that 17E6 is an allosteric inhibitor of alphaV integrins. | ||
| - | + | Atomic basis for the species-specific inhibition of alphaV integrins by monoclonal antibody 17E6 is revealed by the crystal structure of alphaVbeta3 ectodomain-17E6 Fab complex.,Mahalingam B, Van Agthoven JF, Xiong JP, Alonso JL, Adair BD, Rui X, Anand S, Mehrbod M, Mofrad MR, Burger C, Goodman SL, Arnaout MA J Biol Chem. 2014 May 16;289(20):13801-9. doi: 10.1074/jbc.M113.546929. Epub 2014, Apr 1. PMID:24692540<ref>PMID:24692540</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4o02" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Integrin 3D structures|Integrin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Arnaout MA]] | ||
| + | [[Category: Mahalingam B]] | ||
| + | [[Category: Xiong J]] | ||
| + | [[Category: Van Agthoven J]] | ||
Current revision
AlphaVBeta3 integrin in complex with monoclonal antibody FAB fragment.
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