2cmr: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (16 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==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 | <StructureSection load='2cmr' size='340' side='right'caption='[[2cmr]], [[Resolution|resolution]] 2.00Å' 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]] 2Å</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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</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: | [[Category: Large Structures]] | ||
[[Category: Barbato | [[Category: Barbato G]] | ||
[[Category: Bianchi | [[Category: Bianchi E]] | ||
[[Category: Carfi | [[Category: Carfi A]] | ||
[[Category: | [[Category: Di Giovine P]] | ||
[[Category: | [[Category: Geleziunas R]] | ||
[[Category: Hrin | [[Category: Hrin R]] | ||
[[Category: Luftig | [[Category: Luftig MA]] | ||
[[Category: Mattu | [[Category: Mattu M]] | ||
[[Category: Miller | [[Category: Miller MD]] | ||
[[Category: Pessi | [[Category: Pessi A]] | ||
Latest revision as of 17:22, 13 December 2023
Crystal structure of the HIV-1 neutralizing antibody D5 Fab bound to the gp41 inner-core mimetic 5-helixCrystal structure of the HIV-1 neutralizing antibody D5 Fab bound to the gp41 inner-core mimetic 5-helix
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedElicitation 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||