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Yorodumi- PDB-6wps: Structure of the SARS-CoV-2 spike glycoprotein in complex with th... -
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-Basic information
Entry | Database: PDB / ID: 6wps | |||||||||
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Title | Structure of the SARS-CoV-2 spike glycoprotein in complex with the S309 neutralizing antibody Fab fragment | |||||||||
Components |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / SARS-CoV / spike glycoprotein / fusion protein / neutralizing antibody / sarbecovirus / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Pinto, D. / Park, Y.J. / Beltramello, M. / Walls, A.C. / Tortorici, M.A. / Bianchi, S. / Jaconi, S. / Culap, K. / Zatta, F. / De Marco, A. ...Pinto, D. / Park, Y.J. / Beltramello, M. / Walls, A.C. / Tortorici, M.A. / Bianchi, S. / Jaconi, S. / Culap, K. / Zatta, F. / De Marco, A. / Peter, A. / Guarino, B. / Spreafico, R. / Cameroni, E. / Case, J.B. / Chen, R.E. / Havenar-Daughton, C. / Snell, G. / Virgin, H.W. / Lanzavecchia, A. / Diamond, M.S. / Fink, K. / Veesler, D. / Corti, D. / Seattle Structural Genomics Center for Infectious Disease (SSGCID) | |||||||||
Funding support | United States, 1items
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Citation | Journal: Nature / Year: 2020 Title: Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / ...Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / Barbara Guarino / Roberto Spreafico / Elisabetta Cameroni / James Brett Case / Rita E Chen / Colin Havenar-Daughton / Gyorgy Snell / Amalio Telenti / Herbert W Virgin / Antonio Lanzavecchia / Michael S Diamond / Katja Fink / David Veesler / Davide Corti / Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in ...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease. #1: Journal: bioRxiv / Year: 2020 Title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody. Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / ...Authors: Dora Pinto / Young-Jun Park / Martina Beltramello / Alexandra C Walls / M Alejandra Tortorici / Siro Bianchi / Stefano Jaconi / Katja Culap / Fabrizia Zatta / Anna De Marco / Alessia Peter / Barbara Guarino / Roberto Spreafico / Elisabetta Cameroni / James Brett Case / Rita E Chen / Colin Havenar-Daughton / Gyorgy Snell / Amalio Telenti / Herbert W Virgin / Antonio Lanzavecchia / Michael S Diamond / Katja Fink / David Veesler / Davide Corti Abstract: SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths . Vaccine and therapeutic discovery ...SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths . Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6wps.cif.gz | 703 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6wps.ent.gz | 574.4 KB | Display | PDB format |
PDBx/mmJSON format | 6wps.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wps_validation.pdf.gz | 3.2 MB | Display | wwPDB validaton report |
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Full document | 6wps_full_validation.pdf.gz | 3.2 MB | Display | |
Data in XML | 6wps_validation.xml.gz | 95.1 KB | Display | |
Data in CIF | 6wps_validation.cif.gz | 147.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wp/6wps ftp://data.pdbj.org/pub/pdb/validation_reports/wp/6wps | HTTPS FTP |
-Related structure data
Related structure data | 21864MC 6wptC 6ws6C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 3 molecules ABE
#1: Protein | Mass: 141532.797 Da / Num. of mol.: 3 Fragment: signaling sequence + ectodomain (UNP residues 14-1211) + foldon trimerization domain + TEV cleavage site + His-tag,signaling sequence + ectodomain (UNP residues 14-1211) + foldon ...Fragment: signaling sequence + ectodomain (UNP residues 14-1211) + foldon trimerization domain + TEV cleavage site + His-tag,signaling sequence + ectodomain (UNP residues 14-1211) + foldon trimerization domain + TEV cleavage site + His-tag Mutation: R701S,R702G,R704G,K1005P,V1005P Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
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-Antibody , 2 types, 6 molecules HCFLDG
#2: Antibody | Mass: 14005.526 Da / Num. of mol.: 3 / Fragment: Fab Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11444.677 Da / Num. of mol.: 3 / Fragment: Fab Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Sugars , 3 types, 48 molecules
#4: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 70 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 168449 / Symmetry type: POINT | ||||||||||||||||||
Atomic model building | Protocol: OTHER | ||||||||||||||||||
Atomic model building | PDB-ID: 6VXX | ||||||||||||||||||
Refinement | Highest resolution: 3.1 Å |