7r40
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Structure of the SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment== | ==Structure of the SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment== | ||
| - | <StructureSection load='7r40' size='340' side='right'caption='[[7r40]]' scene=''> | + | <StructureSection load='7r40' size='340' side='right'caption='[[7r40]], [[Resolution|resolution]] 2.90Å' 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=7R40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R40 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7r40]] is a 9 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=7R40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R40 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=7r40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r40 OCA], [https://pdbe.org/7r40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r40 RCSB], [https://www.ebi.ac.uk/pdbsum/7r40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r40 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]] 2.9Å</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=7r40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r40 OCA], [https://pdbe.org/7r40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r40 RCSB], [https://www.ebi.ac.uk/pdbsum/7r40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r40 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 evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity. | ||
| + | |||
| + | An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern.,Du W, Hurdiss DL, Drabek D, Mykytyn AZ, Kaiser FK, Gonzalez-Hernandez M, Munoz-Santos D, Lamers MM, van Haperen R, Li W, Drulyte I, Wang C, Sola I, Armando F, Beythien G, Ciurkiewicz M, Baumgartner W, Guilfoyle K, Smits T, van der Lee J, van Kuppeveld FJM, van Amerongen G, Haagmans BL, Enjuanes L, Osterhaus ADME, Grosveld F, Bosch BJ Sci Immunol. 2022 Jul 29;7(73):eabp9312. doi: 10.1126/sciimmunol.abp9312. Epub, 2022 Jul 29. PMID:35471062<ref>PMID:35471062</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7r40" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Antibody 3D structures|Antibody 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Hurdiss DL]] | [[Category: Hurdiss DL]] | ||
Revision as of 16:08, 13 December 2023
Structure of the SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment
| |||||||||||
