8fxc: Difference between revisions

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'''Unreleased structure'''


The entry 8fxc is ON HOLD
==SARS-CoV-2 BQ.1.1 spike RBD bound to the human ACE2 ectodomain and the S309 neutralizing antibody Fab fragment==
<StructureSection load='8fxc' size='340' side='right'caption='[[8fxc]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fxc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=8FXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FXC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8fxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fxc OCA], [https://pdbe.org/8fxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fxc RCSB], [https://www.ebi.ac.uk/pdbsum/8fxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fxc ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain(1) (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting.


Authors:  
Neutralization, effector function and immune imprinting of Omicron variants.,Addetia A, Piccoli L, Case JB, Park YJ, Beltramello M, Guarino B, Dang H, de Melo GD, Pinto D, Sprouse K, Scheaffer SM, Bassi J, Silacci-Fregni C, Muoio F, Dini M, Vincenzetti L, Acosta R, Johnson D, Subramanian S, Saliba C, Giurdanella M, Lombardo G, Leoni G, Culap K, McAlister C, Rajesh A, Dellota E Jr, Zhou J, Farhat N, Bohan D, Noack J, Chen A, Lempp FA, Quispe J, Kergoat L, Larrous F, Cameroni E, Whitener B, Giannini O, Cippa P, Ceschi A, Ferrari P, Franzetti-Pellanda A, Biggiogero M, Garzoni C, Zappi S, Bernasconi L, Kim MJ, Rosen LE, Schnell G, Czudnochowski N, Benigni F, Franko N, Logue JK, Yoshiyama C, Stewart C, Chu H, Bourhy H, Schmid MA, Purcell LA, Snell G, Lanzavecchia A, Diamond MS, Corti D, Veesler D Nature. 2023 Sep;621(7979):592-601. doi: 10.1038/s41586-023-06487-6. Epub 2023 , Aug 30. PMID:37648855<ref>PMID:37648855</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8fxc" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Park YJ]]
[[Category: Veesler D]]

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