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==== | ==Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibodies CV07-287 and COVA1-16== | ||
<StructureSection load='7s5r' size='340' side='right'caption='[[7s5r]]' scene=''> | <StructureSection load='7s5r' size='340' side='right'caption='[[7s5r]], [[Resolution|resolution]] 2.45Å' 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'>[[7s5r]] is a 5 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=7S5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S5R 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=7s5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s5r OCA], [https://pdbe.org/7s5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s5r RCSB], [https://www.ebi.ac.uk/pdbsum/7s5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s5r 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]] 2.45Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7s5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s5r OCA], [https://pdbe.org/7s5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s5r RCSB], [https://www.ebi.ac.uk/pdbsum/7s5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s5r 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 == | |||
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics. | |||
SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies.,Reincke SM, Yuan M, Kornau HC, Corman VM, van Hoof S, Sanchez-Sendin E, Ramberger M, Yu W, Hua Y, Tien H, Schmidt ML, Schwarz T, Jeworowski LM, Brandl SE, Rasmussen HF, Homeyer MA, Stoffler L, Barner M, Kunkel D, Huo S, Horler J, von Wardenburg N, Kroidl I, Eser TM, Wieser A, Geldmacher C, Hoelscher M, Ganzer H, Weiss G, Schmitz D, Drosten C, Pruss H, Wilson IA, Kreye J Science. 2022 Feb 18;375(6582):782-787. doi: 10.1126/science.abm5835. Epub 2022 , Jan 25. PMID:35076281<ref>PMID:35076281</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7s5r" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Wilson IA]] | |||
[[Category: Yuan M]] | |||
Latest revision as of 14:28, 23 October 2024
Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibodies CV07-287 and COVA1-16Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibodies CV07-287 and COVA1-16
Structural highlights
FunctionSPIKE_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][1] [2] [3] 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] Publication Abstract from PubMedSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics. SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies.,Reincke SM, Yuan M, Kornau HC, Corman VM, van Hoof S, Sanchez-Sendin E, Ramberger M, Yu W, Hua Y, Tien H, Schmidt ML, Schwarz T, Jeworowski LM, Brandl SE, Rasmussen HF, Homeyer MA, Stoffler L, Barner M, Kunkel D, Huo S, Horler J, von Wardenburg N, Kroidl I, Eser TM, Wieser A, Geldmacher C, Hoelscher M, Ganzer H, Weiss G, Schmitz D, Drosten C, Pruss H, Wilson IA, Kreye J Science. 2022 Feb 18;375(6582):782-787. doi: 10.1126/science.abm5835. Epub 2022 , Jan 25. PMID:35076281[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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