7cn9: Difference between revisions
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==Cryo-EM structure of SARS-CoV-2 Spike ectodomain== | ==Cryo-EM structure of SARS-CoV-2 Spike ectodomain== | ||
<StructureSection load='7cn9' size='340' side='right'caption='[[7cn9]]' scene=''> | <StructureSection load='7cn9' size='340' side='right'caption='[[7cn9]], [[Resolution|resolution]] 4.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CN9 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[7cn9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CN9 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=7cn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cn9 OCA], [https://pdbe.org/7cn9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cn9 RCSB], [https://www.ebi.ac.uk/pdbsum/7cn9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cn9 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19. | |||
A Carbohydrate-Binding Protein from the Edible Lablab Beans Effectively Blocks the Infections of Influenza Viruses and SARS-CoV-2.,Liu YM, Shahed-Al-Mahmud M, Chen X, Chen TH, Liao KS, Lo JM, Wu YM, Ho MC, Wu CY, Wong CH, Jan JT, Ma C Cell Rep. 2020 Aug 11;32(6):108016. doi: 10.1016/j.celrep.2020.108016. Epub 2020 , Jul 24. PMID:32755598<ref>PMID:32755598</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7cn9" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: 2019-ncov]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chang Y]] | [[Category: Chang, Y]] | ||
[[Category: Chen T]] | [[Category: Chen, T]] | ||
[[Category: Chen X]] | [[Category: Chen, X]] | ||
[[Category: Ho M]] | [[Category: Ho, M]] | ||
[[Category: Huang H]] | [[Category: Huang, H]] | ||
[[Category: Lo | [[Category: Lo, J M]] | ||
[[Category: Ma C]] | [[Category: Ma, C]] | ||
[[Category: Wang C]] | [[Category: Wang, C]] | ||
[[Category: Wu Y]] | [[Category: Wu, Y]] | ||
[[Category: Fully glycosylated]] | |||
[[Category: Sars-cov-2]] | |||
[[Category: Spike]] | |||
[[Category: Viral protein]] | |||