2cmr

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[[Image:2cmr.gif|left|200px]]<br />
 
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<applet load="2cmr" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2cmr, resolution 2.00&Aring;" />
 
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'''CRYSTAL STRUCTURE OF THE HIV-1 NEUTRALIZING ANTIBODY D5 FAB BOUND TO THE GP41 INNER-CORE MIMETIC 5-HELIX'''<br />
 
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==Overview==
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==Crystal structure of the HIV-1 neutralizing antibody D5 Fab bound to the gp41 inner-core mimetic 5-helix==
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Elicitation of potent and broadly neutralizing antibodies is an important, goal in designing an effective human immunodeficiency virus-1 (HIV-1), vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and, structurally conserved target for therapeutics. Here we report the, 2.0-A-resolution crystal structure of the complex between the, antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and, 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend, on residues in the D5 CDR H2 loop protruding into the conserved gp41, hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41, residues. Kinetic analysis of D5 mutants with perturbed D5-gp41, interactions suggests that D5 persistence at the fusion intermediate is, crucial for neutralization. Thus, our data validate the gp41 N-peptide, trimer fusion intermediate as a target for neutralizing antibodies and, provide a template for identification of more potent and broadly, neutralizing molecules.
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<StructureSection load='2cmr' size='340' side='right'caption='[[2cmr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2cmr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CMR FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cmr OCA], [https://pdbe.org/2cmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cmr RCSB], [https://www.ebi.ac.uk/pdbsum/2cmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cmr ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/D0VWW0_9HIV1 D0VWW0_9HIV1]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cm/2cmr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cmr ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Elicitation of potent and broadly neutralizing antibodies is an important goal in designing an effective human immunodeficiency virus-1 (HIV-1) vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and structurally conserved target for therapeutics. Here we report the 2.0-A-resolution crystal structure of the complex between the antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend on residues in the D5 CDR H2 loop protruding into the conserved gp41 hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41 residues. Kinetic analysis of D5 mutants with perturbed D5-gp41 interactions suggests that D5 persistence at the fusion intermediate is crucial for neutralization. Thus, our data validate the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules.
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==About this Structure==
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Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody.,Luftig MA, Mattu M, Di Giovine P, Geleziunas R, Hrin R, Barbato G, Bianchi E, Miller MD, Pessi A, Carfi A Nat Struct Mol Biol. 2006 Aug;13(8):740-7. Epub 2006 Jul 23. PMID:16862157<ref>PMID:16862157</ref>
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2CMR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CMR OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody., Luftig MA, Mattu M, Di Giovine P, Geleziunas R, Hrin R, Barbato G, Bianchi E, Miller MD, Pessi A, Carfi A, Nat Struct Mol Biol. 2006 Aug;13(8):740-7. Epub 2006 Jul 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16862157 16862157]
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</div>
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<div class="pdbe-citations 2cmr" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[3D structures of human antibody|3D structures of human antibody]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Barbato, G.]]
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[[Category: Barbato G]]
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[[Category: Bianchi, E.]]
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[[Category: Bianchi E]]
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[[Category: Carfi, A.]]
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[[Category: Carfi A]]
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[[Category: Geleziunas, R.]]
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[[Category: Di Giovine P]]
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[[Category: Giovine, P.Di.]]
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[[Category: Geleziunas R]]
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[[Category: Hrin, R.]]
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[[Category: Hrin R]]
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[[Category: Luftig, M.A.]]
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[[Category: Luftig MA]]
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[[Category: Mattu, M.]]
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[[Category: Mattu M]]
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[[Category: Miller, M.D.]]
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[[Category: Miller MD]]
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[[Category: Pessi, A.]]
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[[Category: Pessi A]]
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[[Category: GOL]]
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[[Category: aids]]
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[[Category: envelope protein]]
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[[Category: gp41]]
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[[Category: hiv]]
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[[Category: immunoglobulin]]
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[[Category: immunoglobulin complex]]
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[[Category: immunoglobulin domain]]
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[[Category: membrane]]
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[[Category: mhc i]]
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[[Category: neutralization]]
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[[Category: transmembrane]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 18:13:44 2007''
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Current revision

Crystal structure of the HIV-1 neutralizing antibody D5 Fab bound to the gp41 inner-core mimetic 5-helix

PDB ID 2cmr

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