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==Anti-HIV-1 Fab Fab 2G12 + Man4 re-refinement== | |||
<StructureSection load='6msy' size='340' side='right'caption='[[6msy]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6msy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1zls 1zls]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MSY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MSY FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6msy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6msy OCA], [http://pdbe.org/6msy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6msy RCSB], [http://www.ebi.ac.uk/pdbsum/6msy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6msy ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. A prior crystal structure of 2G12 in complex with Man(9)GlcNAc(2) highlighted the central importance of the D1 arm in antibody binding. To characterize the specificity of 2G12 more precisely, we performed solution-phase ELISA, carbohydrate microarray analysis, and cocrystallized Fab 2G12 with four different oligomannose derivatives (Man(4), Man(5), Man(7), and Man(8)) that compete with gp120 for binding to 2G12. Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man(9)GlcNAc(2) moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. These results have important consequences for the design of immunogens to elicit 2G12-like neutralizing antibodies as a component of an HIV vaccine. | |||
Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12.,Calarese DA, Lee HK, Huang CY, Best MD, Astronomo RD, Stanfield RL, Katinger H, Burton DR, Wong CH, Wilson IA Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13372-7. Epub 2005 Sep 7. PMID:16174734<ref>PMID:16174734</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Stanfield, R | <div class="pdbe-citations 6msy" style="background-color:#fffaf0;"></div> | ||
[[Category: Wilson, I | |||
[[Category: | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Calarese, D A]] | |||
[[Category: Stanfield, R L]] | |||
[[Category: Wilson, I A]] | |||
[[Category: Anti-carbohydrate]] | |||
[[Category: Domain-swapping]] | |||
[[Category: Hiv neutralizing antibody]] | |||
[[Category: Hiv-1 carbohydrate broadly neutralizing antibody]] | |||
[[Category: Immune system]] | |||
Revision as of 14:29, 1 January 2020
Anti-HIV-1 Fab Fab 2G12 + Man4 re-refinementAnti-HIV-1 Fab Fab 2G12 + Man4 re-refinement
Structural highlights
Publication Abstract from PubMedHuman antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. A prior crystal structure of 2G12 in complex with Man(9)GlcNAc(2) highlighted the central importance of the D1 arm in antibody binding. To characterize the specificity of 2G12 more precisely, we performed solution-phase ELISA, carbohydrate microarray analysis, and cocrystallized Fab 2G12 with four different oligomannose derivatives (Man(4), Man(5), Man(7), and Man(8)) that compete with gp120 for binding to 2G12. Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man(9)GlcNAc(2) moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. These results have important consequences for the design of immunogens to elicit 2G12-like neutralizing antibodies as a component of an HIV vaccine. Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12.,Calarese DA, Lee HK, Huang CY, Best MD, Astronomo RD, Stanfield RL, Katinger H, Burton DR, Wong CH, Wilson IA Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13372-7. Epub 2005 Sep 7. PMID:16174734[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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