7p7b
From Proteopedia
(Difference between revisions)
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| - | ==SARS-CoV-2 spike protein in complex with sybody | + | ==SARS-CoV-2 spike protein in complex with sybody no68 in a 1up/2down conformation== |
| - | <StructureSection load='7p7b' size='340' side='right'caption='[[7p7b]]' scene=''> | + | <StructureSection load='7p7b' size='340' side='right'caption='[[7p7b]], [[Resolution|resolution]] 3.13Å' 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=7P7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P7B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7p7b]] 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=7P7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P7B FirstGlance]. <br> |
| - | </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=7p7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p7b OCA], [https://pdbe.org/7p7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p7b RCSB], [https://www.ebi.ac.uk/pdbsum/7p7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p7b ProSAT]</span></td></tr> | + | </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=7p7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p7b OCA], [https://pdbe.org/7p7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p7b RCSB], [https://www.ebi.ac.uk/pdbsum/7p7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p7b 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 ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair, Sb#15 and Sb#68, that can bind simultaneously to the SARS-CoV-2 spike RBD and efficiently neutralize pseudotyped and live viruses by interfering with ACE2 interaction. Cryo-EM confirms that Sb#15 and Sb#68 engage two spatially discrete epitopes, influencing rational design of bispecific and tri-bispecific fusion constructs that exhibit up to 100- and 1,000-fold increase in neutralization potency, respectively. Cryo-EM of the sybody-spike complex additionally reveals a novel up-out RBD conformation. While resistant viruses emerge rapidly in the presence of single binders, no escape variants are observed in the presence of the bispecific sybody. The multivalent bispecific constructs further increase the neutralization potency against globally circulating SARS-CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the potential development of therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants. | ||
| + | |||
| + | Biparatopic sybodies neutralize SARS-CoV-2 variants of concern and mitigate drug resistance.,Walter JD, Scherer M, Hutter CAJ, Garaeva AA, Zimmermann I, Wyss M, Rheinberger J, Ruedin Y, Earp JC, Egloff P, Sorgenfrei M, Hurlimann LM, Gonda I, Meier G, Remm S, Thavarasah S, van Geest G, Bruggmann R, Zimmer G, Slotboom DJ, Paulino C, Plattet P, Seeger MA EMBO Rep. 2022 Mar 7:e54199. doi: 10.15252/embr.202154199. PMID:35253970<ref>PMID:35253970</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7p7b" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: 2019-ncov]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Earp | + | [[Category: Earp, J C]] |
| - | [[Category: Egloff P]] | + | [[Category: Egloff, P]] |
| - | [[Category: Garaeva | + | [[Category: Garaeva, A A]] |
| - | [[Category: Gonda I]] | + | [[Category: Gonda, I]] |
| - | [[Category: Huerlimann | + | [[Category: Huerlimann, L M]] |
| - | [[Category: Hutter | + | [[Category: Hutter, C A.J]] |
| - | [[Category: Meier G]] | + | [[Category: Meier, G]] |
| - | [[Category: Paulino C]] | + | [[Category: Paulino, C]] |
| - | [[Category: Plattet P]] | + | [[Category: Plattet, P]] |
| - | [[Category: Remm S]] | + | [[Category: Remm, S]] |
| - | [[Category: Rheinberger J]] | + | [[Category: Rheinberger, J]] |
| - | [[Category: Ruedin Y]] | + | [[Category: Ruedin, Y]] |
| - | [[Category: Scherer M]] | + | [[Category: Scherer, M]] |
| - | [[Category: Seeger | + | [[Category: Seeger, M A]] |
| - | [[Category: Slotboom | + | [[Category: Slotboom, D J]] |
| - | [[Category: Sorgenfrei M]] | + | [[Category: Sorgenfrei, M]] |
| - | [[Category: Thavarasah S]] | + | [[Category: Thavarasah, S]] |
| - | [[Category: Walter | + | [[Category: Walter, J D]] |
| - | [[Category: Wyss M]] | + | [[Category: Wyss, M]] |
| - | [[Category: Zimmer G]] | + | [[Category: Zimmer, G]] |
| - | [[Category: Zimmermann I]] | + | [[Category: Zimmermann, I]] |
| + | [[Category: Sars-cov-2 spike protein sybody]] | ||
| + | [[Category: Viral protein]] | ||
Revision as of 07:19, 16 March 2022
SARS-CoV-2 spike protein in complex with sybody no68 in a 1up/2down conformation
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Categories: 2019-ncov | Large Structures | Earp, J C | Egloff, P | Garaeva, A A | Gonda, I | Huerlimann, L M | Hutter, C A.J | Meier, G | Paulino, C | Plattet, P | Remm, S | Rheinberger, J | Ruedin, Y | Scherer, M | Seeger, M A | Slotboom, D J | Sorgenfrei, M | Thavarasah, S | Walter, J D | Wyss, M | Zimmer, G | Zimmermann, I | Sars-cov-2 spike protein sybody | Viral protein
