7nkt
From Proteopedia
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| - | ==== | + | ==RBD domain of SARS-CoV2 in complex with neutralizing nanobody NM1226== |
| - | <StructureSection load='7nkt' size='340' side='right'caption='[[7nkt]]' scene=''> | + | <StructureSection load='7nkt' size='340' side='right'caption='[[7nkt]], [[Resolution|resolution]] 2.30Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7nkt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NKT 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=7nkt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nkt OCA], [https://pdbe.org/7nkt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nkt RCSB], [https://www.ebi.ac.uk/pdbsum/7nkt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nkt ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7nkt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nkt OCA], [https://pdbe.org/7nkt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nkt RCSB], [https://www.ebi.ac.uk/pdbsum/7nkt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nkt 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 == | ||
| + | In light of the COVID-19 pandemic, there is an ongoing need for diagnostic tools to monitor the immune status of large patient cohorts and the effectiveness of vaccination campaigns. Here, we present 11 unique nanobodies (Nbs) specific for the SARS-CoV-2 spike receptor-binding domain (RBD), of which 8 Nbs potently inhibit the interaction of RBD with angiotensin-converting enzyme 2 (ACE2) as the major viral docking site. Following detailed epitope mapping and structural analysis, we select two inhibitory Nbs, one of which binds an epitope inside and one of which binds an epitope outside the RBD:ACE2 interface. Based on these, we generate a biparatopic nanobody (bipNb) with viral neutralization efficacy in the picomolar range. Using bipNb as a surrogate, we establish a competitive multiplex binding assay ("NeutrobodyPlex") for detailed analysis of the presence and performance of neutralizing RBD-binding antibodies in serum of convalescent or vaccinated patients. We demonstrate that NeutrobodyPlex enables high-throughput screening and detailed analysis of neutralizing immune responses in infected or vaccinated individuals, to monitor immune status or to guide vaccine design. | ||
| + | |||
| + | NeutrobodyPlex-monitoring SARS-CoV-2 neutralizing immune responses using nanobodies.,Wagner TR, Ostertag E, Kaiser PD, Gramlich M, Ruetalo N, Junker D, Haering J, Traenkle B, Becker M, Dulovic A, Schweizer H, Nueske S, Scholz A, Zeck A, Schenke-Layland K, Nelde A, Strengert M, Walz JS, Zocher G, Stehle T, Schindler M, Schneiderhan-Marra N, Rothbauer U EMBO Rep. 2021 May 5;22(5):e52325. doi: 10.15252/embr.202052325. Epub 2021 Apr , 27. PMID:33904225<ref>PMID:33904225</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7nkt" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Spike protein 3D structures|Spike protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Severe acute respiratory syndrome coronavirus 2]] |
| + | [[Category: Vicugna pacos]] | ||
| + | [[Category: Ostertag E]] | ||
| + | [[Category: Stehle T]] | ||
| + | [[Category: Zocher G]] | ||
Revision as of 12:35, 1 February 2024
RBD domain of SARS-CoV2 in complex with neutralizing nanobody NM1226
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