View source for 7lm9


==Crystal structure of SARS-CoV spike protein receptor-binding domain in complex with a cross-neutralizing antibody CV38-142 Fab isolated from COVID-19 patient==
<StructureSection load='7lm9' size='340' side='right'caption='[[7lm9]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lm9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/SARS_coronavirus_MA15 SARS coronavirus MA15]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LM9 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]] 1.53&#8491;</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <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=7lm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lm9 OCA], [https://pdbe.org/7lm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lm9 RCSB], [https://www.ebi.ac.uk/pdbsum/7lm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lm9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D2E265_SARS D2E265_SARS] Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099]  Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]  Spike protein S2: mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099]
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== Publication Abstract from PubMed ==
Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection.,Liu H, Yuan M, Huang D, Bangaru S, Zhao F, Lee CD, Peng L, Barman S, Zhu X, Nemazee D, Burton DR, van Gils MJ, Sanders RW, Kornau HC, Reincke SM, Pruss H, Kreye J, Wu NC, Ward AB, Wilson IA Cell Host Microbe. 2021 May 12;29(5):806-818.e6. doi: 10.1016/j.chom.2021.04.005. , Epub 2021 Apr 15. PMID:33894127<ref>PMID:33894127</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7lm9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: SARS coronavirus MA15]]
[[Category: Liu H]]
[[Category: Wilson IA]]
[[Category: Yuan M]]
[[Category: Zhu X]]