7wi0: Difference between revisions

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-====
+==SARS-CoV-2 Omicron variant spike in complex with three human neutralizing antibodies==
-<StructureSection load='7wi0' size='340' side='right'caption='[[7wi0]]' scene=''>
+<StructureSection load='7wi0' size='340' side='right'caption='[[7wi0]], [[Resolution|resolution]] 3.82&Aring;' scene=''>
 == 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'>[[7wi0]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WI0 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=7wi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wi0 OCA], [https://pdbe.org/7wi0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wi0 RCSB], [https://www.ebi.ac.uk/pdbsum/7wi0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wi0 ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.82&#8491;</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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7wi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wi0 OCA], [https://pdbe.org/7wi0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wi0 RCSB], [https://www.ebi.ac.uk/pdbsum/7wi0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wi0 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 ==
+The rapidly spreading Omicron variant is highly resistant to vaccines, convalescent sera, and neutralizing antibodies (nAbs), highlighting the urgent need for potent therapeutic nAbs. Here, a panel of human nAbs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent patients show diverse neutralization against Omicron, of which XMA01 and XMA04 maintain nanomolar affinities and excellent neutralization (half maximal inhibitory concentration [IC50]: approximately 20 ng/mL). nAb XMA09 shows weak but unattenuated neutralization against all variants of concern (VOCs) as well as SARS-CoV. Structural analysis reveals that the above three antibodies could synergistically bind to the receptor-binding domains (RBDs) of both wild-type and Omicron spikes and defines the critical determinants for nAb-mediated broad neutralizations. Three nAbs confer synergistic neutralization against Omicron, resulting from the inter-antibody interaction between XMA04 and XMA01(or XMA09). Furthermore, the XMA01/XMA04 cocktail provides synergistic protection against Beta and Omicron variant infections in hamsters. In summary, our results provide insights for the rational design of antibody cocktail therapeutics or universal vaccines against Omicron.
+Three SARS-CoV-2 antibodies provide broad and synergistic neutralization against variants of concern, including Omicron.,Wang S, Sun H, Zhang Y, Yuan L, Wang Y, Zhang T, Wang S, Zhang J, Yu H, Xiong H, Tang Z, Liu L, Huang Y, Chen X, Li T, Ying D, Liu C, Chen Z, Yuan Q, Zhang J, Cheng T, Li S, Guan Y, Zheng Q, Zheng Z, Xia N Cell Rep. 2022 May 24;39(8):110862. doi: 10.1016/j.celrep.2022.110862. Epub 2022 , May 8. PMID:35594869<ref>PMID:35594869</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7wi0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Spike protein 3D structures|Spike protein 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Z-disk]]
+[[Category: Li S]]
+[[Category: Sun H]]
+[[Category: Wang S]]
+[[Category: Zheng Q]]
+[[Category: Zheng Z]]