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==Structure of the anti-HIV-1 neutralizing antibody BG24 Fab fragment== | ==Structure of the anti-HIV-1 neutralizing antibody BG24 Fab fragment== | ||
<StructureSection load='7uce' size='340' side='right'caption='[[7uce]]' scene=''> | <StructureSection load='7uce' size='340' side='right'caption='[[7uce]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UCE FirstGlance]. <br> | <table><tr><td colspan='2'>[[7uce]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UCE FirstGlance]. <br> | ||
</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=7uce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uce OCA], [https://pdbe.org/7uce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uce RCSB], [https://www.ebi.ac.uk/pdbsum/7uce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uce ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7uce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uce OCA], [https://pdbe.org/7uce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uce RCSB], [https://www.ebi.ac.uk/pdbsum/7uce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uce ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-A x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. | |||
A naturally arising broad and potent CD4-binding site antibody with low somatic mutation.,Barnes CO, Schoofs T, Gnanapragasam PNP, Golijanin J, Huey-Tubman KE, Gruell H, Schommers P, Suh-Toma N, Lee YE, Cetrulo Lorenzi JC, Piechocka-Trocha A, Scheid JF, West AP Jr, Walker BD, Seaman MS, Klein F, Nussenzweig MC, Bjorkman PJ Sci Adv. 2022 Aug 12;8(32):eabp8155. doi: 10.1126/sciadv.abp8155. Epub 2022 Aug, 12. PMID:35960796<ref>PMID:35960796</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7uce" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Barnes CO]] | [[Category: Barnes CO]] | ||
[[Category: Bjorkman PJ]] | [[Category: Bjorkman PJ]] | ||
Latest revision as of 20:13, 18 October 2023
Structure of the anti-HIV-1 neutralizing antibody BG24 Fab fragmentStructure of the anti-HIV-1 neutralizing antibody BG24 Fab fragment
Structural highlights
Publication Abstract from PubMedThe induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-A x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. A naturally arising broad and potent CD4-binding site antibody with low somatic mutation.,Barnes CO, Schoofs T, Gnanapragasam PNP, Golijanin J, Huey-Tubman KE, Gruell H, Schommers P, Suh-Toma N, Lee YE, Cetrulo Lorenzi JC, Piechocka-Trocha A, Scheid JF, West AP Jr, Walker BD, Seaman MS, Klein F, Nussenzweig MC, Bjorkman PJ Sci Adv. 2022 Aug 12;8(32):eabp8155. doi: 10.1126/sciadv.abp8155. Epub 2022 Aug, 12. PMID:35960796[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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