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==Crystal structure of broadly and potently neutralizing antibody VRC-CH31 in complex with HIV-1 clade A/E gp120 93TH057== | |||
<StructureSection load='4lsp' size='340' side='right' caption='[[4lsp]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lsp]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LSP OCA]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ngb|3ngb]], [[3se8|3se8]], [[3se9|3se9]], [[4jpv|4jpv]], [[4jpw|4jpw]], [[4j6r|4j6r]], [[4jb9|4jb9]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">env ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lsp RCSB], [http://www.ebi.ac.uk/pdbsum/4lsp PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population. | |||
Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies.,Zhou T, Zhu J, Wu X, Moquin S, Zhang B, Acharya P, Georgiev IS, Altae-Tran HR, Chuang GY, Joyce MG, Do Kwon Y, Longo NS, Louder MK, Luongo T, McKee K, Schramm CA, Skinner J, Yang Y, Yang Z, Zhang Z, Zheng A, Bonsignori M, Haynes BF, Scheid JF, Nussenzweig MC, Simek M, Burton DR, Koff WC, Mullikin JC, Connors M, Shapiro L, Nabel GJ, Mascola JR, Kwong PD Immunity. 2013 Aug 22;39(2):245-58. doi: 10.1016/j.immuni.2013.04.012. Epub 2013 , Aug 1. PMID:23911655<ref>PMID:23911655</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: | == References == | ||
[[Category: Human | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: 9hiv1]] | |||
[[Category: Human]] | |||
[[Category: Kwong, P D.]] | [[Category: Kwong, P D.]] | ||
[[Category: Moquin, S.]] | [[Category: Moquin, S.]] | ||
Revision as of 09:50, 7 May 2014
Crystal structure of broadly and potently neutralizing antibody VRC-CH31 in complex with HIV-1 clade A/E gp120 93TH057Crystal structure of broadly and potently neutralizing antibody VRC-CH31 in complex with HIV-1 clade A/E gp120 93TH057
Structural highlights
Publication Abstract from PubMedAntibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population. Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies.,Zhou T, Zhu J, Wu X, Moquin S, Zhang B, Acharya P, Georgiev IS, Altae-Tran HR, Chuang GY, Joyce MG, Do Kwon Y, Longo NS, Louder MK, Luongo T, McKee K, Schramm CA, Skinner J, Yang Y, Yang Z, Zhang Z, Zheng A, Bonsignori M, Haynes BF, Scheid JF, Nussenzweig MC, Simek M, Burton DR, Koff WC, Mullikin JC, Connors M, Shapiro L, Nabel GJ, Mascola JR, Kwong PD Immunity. 2013 Aug 22;39(2):245-58. doi: 10.1016/j.immuni.2013.04.012. Epub 2013 , Aug 1. PMID:23911655[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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