8xlm: Difference between revisions
m Protected "8xlm" [edit=sysop:move=sysop] |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Structure of the SARS-CoV-2 EG.5.1 spike glycoprotein in complex with ACE2 (1-up state)== | ||
<StructureSection load='8xlm' size='340' side='right'caption='[[8xlm]], [[Resolution|resolution]] 3.22Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8xlm]] 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=8XLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XLM 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]] 3.22Å</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=8xlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xlm OCA], [https://pdbe.org/8xlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xlm RCSB], [https://www.ebi.ac.uk/pdbsum/8xlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xlm 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 == | |||
In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population. | |||
Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.,Tsujino S, Deguchi S, Nomai T, Padilla-Blanco M, Plianchaisuk A, Wang L, Begum MM, Uriu K, Mizuma K, Nao N, Kojima I, Tsubo T, Li J, Matsumura Y, Nagao M, Oda Y, Tsuda M, Anraku Y, Kita S, Yajima H, Sasaki-Tabata K, Guo Z, Hinay AA Jr, Yoshimatsu K, Yamamoto Y, Nagamoto T, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Nasser H, Jonathan M, Putri O, Kim Y, Chen L, Suzuki R, Tamura T, Maenaka K, Irie T, Matsuno K, Tanaka S, Ito J, Ikeda T, Takayama K, Zahradnik J, Hashiguchi T, Fukuhara T, Sato K Microbiol Immunol. 2024 Jul 4. doi: 10.1111/1348-0421.13165. PMID:38961765<ref>PMID:38961765</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8xlm" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Hashiguchi | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Anraku Y]] | |||
[[Category: Hashiguchi T]] | |||
[[Category: Kita S]] | |||
[[Category: Maenaka K]] | |||
[[Category: Nomai T]] | |||