7uzc: Difference between revisions
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==Structure of the SARS-CoV-2 RBD in complex with the mouse antibody Fab fragment, M8a-34== | |||
<StructureSection load='7uzc' size='340' side='right'caption='[[7uzc]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7uzc]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UZC 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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=7uzc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uzc OCA], [https://pdbe.org/7uzc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uzc RCSB], [https://www.ebi.ac.uk/pdbsum/7uzc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uzc ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs. | |||
Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes.,Fan C, Cohen AA, Park M, Hung AF, Keeffe JR, Gnanapragasam PNP, Lee YE, Gao H, Kakutani LM, Wu Z, Kleanthous H, Malecek KE, Williams JC, Bjorkman PJ Immunity. 2022 Dec 13;55(12):2419-2435.e10. doi: 10.1016/j.immuni.2022.10.019. , Epub 2022 Oct 27. PMID:36370711<ref>PMID:36370711</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Bjorkman | <div class="pdbe-citations 7uzc" style="background-color:#fffaf0;"></div> | ||
[[Category: Fan | |||
==See Also== | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Bjorkman PJ]] | |||
[[Category: Fan C]] | |||
Latest revision as of 12:15, 17 October 2024
Structure of the SARS-CoV-2 RBD in complex with the mouse antibody Fab fragment, M8a-34Structure of the SARS-CoV-2 RBD in complex with the mouse antibody Fab fragment, M8a-34
Structural highlights
Publication Abstract from PubMedIncreased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs. Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes.,Fan C, Cohen AA, Park M, Hung AF, Keeffe JR, Gnanapragasam PNP, Lee YE, Gao H, Kakutani LM, Wu Z, Kleanthous H, Malecek KE, Williams JC, Bjorkman PJ Immunity. 2022 Dec 13;55(12):2419-2435.e10. doi: 10.1016/j.immuni.2022.10.019. , Epub 2022 Oct 27. PMID:36370711[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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