7ryu: Difference between revisions
New page: '''Unreleased structure''' The entry 7ryu is ON HOLD Authors: Yang, Z., Bjorkman, P.J. Description: Anti-HIV neutralizing antibody Ab1303 Fab isolated from sequentially immunized mcaqu... |
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==Anti-HIV neutralizing antibody Ab1303 Fab isolated from sequentially immunized mcaques== | |||
<StructureSection load='7ryu' size='340' side='right'caption='[[7ryu]], [[Resolution|resolution]] 1.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7ryu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RYU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RYU 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]] 1.51Å</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=7ryu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ryu OCA], [https://pdbe.org/7ryu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ryu RCSB], [https://www.ebi.ac.uk/pdbsum/7ryu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ryu ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Broadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an 'occluded-open' conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts. | |||
Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer.,Yang Z, Dam KA, Bridges MD, Hoffmann MAG, DeLaitsch AT, Gristick HB, Escolano A, Gautam R, Martin MA, Nussenzweig MC, Hubbell WL, Bjorkman PJ Nat Commun. 2022 Feb 8;13(1):732. doi: 10.1038/s41467-022-28424-3. PMID:35136084<ref>PMID:35136084</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7ryu" style="background-color:#fffaf0;"></div> | ||
[[Category: Bjorkman | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Macaca mulatta]] | |||
[[Category: Bjorkman PJ]] | |||
[[Category: Yang Z]] |
Latest revision as of 19:40, 18 October 2023
Anti-HIV neutralizing antibody Ab1303 Fab isolated from sequentially immunized mcaquesAnti-HIV neutralizing antibody Ab1303 Fab isolated from sequentially immunized mcaques
Structural highlights
Publication Abstract from PubMedBroadly-neutralizing antibodies (bNAbs) against HIV-1 Env can protect from infection. We characterize Ab1303 and Ab1573, heterologously-neutralizing CD4-binding site (CD4bs) antibodies, isolated from sequentially-immunized macaques. Ab1303/Ab1573 binding is observed only when Env trimers are not constrained in the closed, prefusion conformation. Fab-Env cryo-EM structures show that both antibodies recognize the CD4bs on Env trimer with an 'occluded-open' conformation between closed, as targeted by bNAbs, and fully-open, as recognized by CD4. The occluded-open Env trimer conformation includes outwardly-rotated gp120 subunits, but unlike CD4-bound Envs, does not exhibit V1V2 displacement, 4-stranded gp120 bridging sheet, or co-receptor binding site exposure. Inter-protomer distances within trimers measured by double electron-electron resonance spectroscopy suggest an equilibrium between occluded-open and closed Env conformations, consistent with Ab1303/Ab1573 binding stabilizing an existing conformation. Studies of Ab1303/Ab1573 demonstrate that CD4bs neutralizing antibodies that bind open Env trimers can be raised by immunization, thereby informing immunogen design and antibody therapeutic efforts. Neutralizing antibodies induced in immunized macaques recognize the CD4-binding site on an occluded-open HIV-1 envelope trimer.,Yang Z, Dam KA, Bridges MD, Hoffmann MAG, DeLaitsch AT, Gristick HB, Escolano A, Gautam R, Martin MA, Nussenzweig MC, Hubbell WL, Bjorkman PJ Nat Commun. 2022 Feb 8;13(1):732. doi: 10.1038/s41467-022-28424-3. PMID:35136084[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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