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[[Image:2cmr.gif|left|200px]]<br />
<applet load="2cmr" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2cmr, resolution 2.00&Aring;" />
'''CRYSTAL STRUCTURE OF THE HIV-1 NEUTRALIZING ANTIBODY D5 FAB BOUND TO THE GP41 INNER-CORE MIMETIC 5-HELIX'''<br />


==Overview==
==Crystal structure of the HIV-1 neutralizing antibody D5 Fab bound to the gp41 inner-core mimetic 5-helix==
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.
<StructureSection load='2cmr' size='340' side='right'caption='[[2cmr]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<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>
</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>
<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>
<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>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D0VWW0_9HIV1 D0VWW0_9HIV1]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cm/2cmr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==About this Structure==
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>
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].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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]
</div>
<div class="pdbe-citations 2cmr" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of human antibody|3D structures of human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Barbato, G.]]
[[Category: Barbato G]]
[[Category: Bianchi, E.]]
[[Category: Bianchi E]]
[[Category: Carfi, A.]]
[[Category: Carfi A]]
[[Category: Geleziunas, R.]]
[[Category: Di Giovine P]]
[[Category: Giovine, P.Di.]]
[[Category: Geleziunas R]]
[[Category: Hrin, R.]]
[[Category: Hrin R]]
[[Category: Luftig, M.A.]]
[[Category: Luftig MA]]
[[Category: Mattu, M.]]
[[Category: Mattu M]]
[[Category: Miller, M.D.]]
[[Category: Miller MD]]
[[Category: Pessi, A.]]
[[Category: Pessi A]]
[[Category: GOL]]
[[Category: aids]]
[[Category: envelope protein]]
[[Category: gp41]]
[[Category: hiv]]
[[Category: immunoglobulin]]
[[Category: immunoglobulin complex]]
[[Category: immunoglobulin domain]]
[[Category: membrane]]
[[Category: mhc i]]
[[Category: neutralization]]
[[Category: transmembrane]]
 
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