View source for 7upx


==Three RBD-down state of SARS-CoV-2 D614G spike in complex with the SP1-77 neutralizing antibody Fab fragment (local refinement of the RBD and Fab variable domains)==
<StructureSection load='7upx' size='340' side='right'caption='[[7upx]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7upx]] is a 3 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 Severe acute respiratory syndrome coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UPX 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></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=7upx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7upx OCA], [https://pdbe.org/7upx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7upx RCSB], [https://www.ebi.ac.uk/pdbsum/7upx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7upx ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SARS-CoV-2 Omicron subvariants have generated a worldwide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron subvariants and prepare for new ones, additional means of isolating broad and potent humanized SARS-CoV-2 neutralizing antibodies are desirable. Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human V(H)1-2 heavy chain (HC) and, substantially, a human Vkappa1-33 light chain (LC). Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact CDR3 sequences generated by nontemplated junctional modifications during V(D)J recombination. Immunizing this mouse model with SARS-CoV-2 (Wuhan-Hu-1) spike protein immunogens elicited several V(H)1-2/Vkappa1-33-based neutralizing antibodies that bound RBD in a different mode from each other and from those of many prior patient-derived V(H)1-2-based neutralizing antibodies. Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5. Cryo-EM studies revealed that SP1-77 bound RBD away from the receptor-binding motif via a CDR3-dominated recognition mode. Lattice light-sheet microscopy-based studies showed that SP1-77 did not block ACE2-mediated viral attachment or endocytosis but rather blocked viral-host membrane fusion. The broad and potent SP1-77 neutralization activity and nontraditional mechanism of action suggest that it might have therapeutic potential. Likewise, the SP1-77 binding epitope may inform vaccine strategies. Last, the type of humanized mouse models that we have described may contribute to identifying therapeutic antibodies against future SARS-CoV-2 variants and other pathogens.

An antibody from single human V(H)-rearranging mouse neutralizes all SARS-CoV-2 variants through BA.5 by inhibiting membrane fusion.,Luo S, Zhang J, Kreutzberger AJB, Eaton A, Edwards RJ, Jing C, Dai HQ, Sempowski GD, Cronin K, Parks R, Ye AY, Mansouri K, Barr M, Pishesha N, Williams AC, Vieira Francisco L, Saminathan A, Peng H, Batra H, Bellusci L, Khurana S, Alam SM, Montefiori DC, Saunders KO, Tian M, Ploegh H, Kirchhausen T, Chen B, Haynes BF, Alt FW Sci Immunol. 2022 Oct 28;7(76):eadd5446. doi: 10.1126/sciimmunol.add5446. Epub , 2022 Aug 11. PMID:35951767<ref>PMID:35951767</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus]]
[[Category: Alt F]]
[[Category: Chen B]]
[[Category: Haynes B]]
[[Category: Kirchhausen T]]
[[Category: Kreutzberger A]]
[[Category: Luo S]]
[[Category: Zhang J]]