7whd: Difference between revisions
New page: '''Unreleased structure''' The entry 7whd is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==SARS-CoV-2 spike in complex with the ZB8 neutralizing antibody Fab (2u1d)== | ||
<StructureSection load='7whd' size='340' side='right'caption='[[7whd]], [[Resolution|resolution]] 2.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7whd]] is a 9 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=7WHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WHD 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]] 2.65Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7whd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7whd OCA], [https://pdbe.org/7whd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7whd RCSB], [https://www.ebi.ac.uk/pdbsum/7whd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7whd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref> 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] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury. | |||
SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters(1).,Zhou B, Zhou R, Chan JF, Zeng J, Zhang Q, Yuan S, Liu L, Robinot R, Shan S, Liu N, Ge J, Kwong HY, Zhou D, Xu H, Chan CC, Poon VK, Chu H, Yue M, Kwan KY, Chan CY, Chan CC, Chik KK, Du Z, Au KK, Huang H, Man HO, Cao J, Li C, Wang Z, Zhou J, Song Y, Yeung ML, To KK, Ho DD, Chakrabarti LA, Wang X, Zhang L, Yuen KY, Chen Z Emerg Microbes Infect. 2023 Dec;12(2):2245921. doi: , 10.1080/22221751.2023.2245921. PMID:37542391<ref>PMID:37542391</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7whd" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Ge JW]] | |||
[[Category: Wang XW]] | |||
[[Category: Wang ZY]] | |||
[[Category: Zeng JW]] | |||