8c1v

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'''Unreleased structure'''
 
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The entry 8c1v is ON HOLD until Paper Publication
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==SARS-CoV-2 S-trimer (3 RBDs up) bound to TriSb92, fitted into cryo-EM map==
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<StructureSection load='8c1v' size='340' side='right'caption='[[8c1v]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8c1v]] is a 6 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=8C1V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C1V FirstGlance]. <br>
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</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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8c1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c1v OCA], [https://pdbe.org/8c1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c1v RCSB], [https://www.ebi.ac.uk/pdbsum/8c1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c1v ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.
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Authors: Huiskonen, J.T., Rissanen, I., Hannula, L.
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Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants.,Makela AR, Ugurlu H, Hannula L, Kant R, Salminen P, Fagerlund R, Maki S, Haveri A, Strandin T, Kareinen L, Hepojoki J, Kuivanen S, Levanov L, Pasternack A, Naves RA, Ritvos O, Osterlund P, Sironen T, Vapalahti O, Kipar A, Huiskonen JT, Rissanen I, Saksela K Nat Commun. 2023 Mar 24;14(1):1637. doi: 10.1038/s41467-023-37290-6. PMID:36964125<ref>PMID:36964125</ref>
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Description: SARS-CoV-2 S-trimer (3 RBDs up) bound to TriSb92, fitted into cryo-EM map
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Hannula, L]]
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<div class="pdbe-citations 8c1v" style="background-color:#fffaf0;"></div>
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[[Category: Rissanen, I]]
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== References ==
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[[Category: Huiskonen, J.T]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Severe acute respiratory syndrome coronavirus 2]]
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[[Category: Hannula L]]
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[[Category: Huiskonen JT]]
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[[Category: Rissanen I]]

Revision as of 09:25, 19 April 2023

SARS-CoV-2 S-trimer (3 RBDs up) bound to TriSb92, fitted into cryo-EM map

PDB ID 8c1v

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