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Yorodumi- PDB-6xey: Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to F... -
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-Basic information
Entry | Database: PDB / ID: 6xey | |||||||||
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Title | Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-4 | |||||||||
Components |
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Keywords | VIRAL PROTEIN/Immune System / spike / glycoprotein / antibody / VIRAL PROTEIN / 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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane ...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 / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / entry receptor-mediated virion attachment to host cell / 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 / 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 / membrane / identical protein binding / 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: 3.25 Å | |||||||||
Authors | Rapp, M. / Shapiro, L. / Ho, D.D. | |||||||||
Funding support | China, 1items
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Citation | Journal: Nature / Year: 2020 Title: Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Authors: Lihong Liu / Pengfei Wang / Manoj S Nair / Jian Yu / Micah Rapp / Qian Wang / Yang Luo / Jasper F-W Chan / Vincent Sahi / Amir Figueroa / Xinzheng V Guo / Gabriele Cerutti / Jude Bimela / ...Authors: Lihong Liu / Pengfei Wang / Manoj S Nair / Jian Yu / Micah Rapp / Qian Wang / Yang Luo / Jasper F-W Chan / Vincent Sahi / Amir Figueroa / Xinzheng V Guo / Gabriele Cerutti / Jude Bimela / Jason Gorman / Tongqing Zhou / Zhiwei Chen / Kwok-Yung Yuen / Peter D Kwong / Joseph G Sodroski / Michael T Yin / Zizhang Sheng / Yaoxing Huang / Lawrence Shapiro / David D Ho / Abstract: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy. The discovery and development of virus- ...The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. #1: Journal: bioRxiv / Year: 2020 Title: Potent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike. Abstract: The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach ...The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 , 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, "all RBD-down" conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. | |||||||||
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 | 6xey.cif.gz | 649.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6xey.ent.gz | 536.7 KB | Display | PDB format |
PDBx/mmJSON format | 6xey.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6xey_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
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Full document | 6xey_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 6xey_validation.xml.gz | 109.1 KB | Display | |
Data in CIF | 6xey_validation.cif.gz | 167.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xe/6xey ftp://data.pdbj.org/pub/pdb/validation_reports/xe/6xey | HTTPS FTP |
-Related structure data
Related structure data | 22156MC 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 ABC
#1: Protein | Mass: 142399.375 Da / Num. of mol.: 3 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 FHJGKL
#2: Antibody | Mass: 13711.394 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #3: Antibody | Mass: 11400.429 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: UniProt: A0A5C2GJG2 |
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-Sugars , 4 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: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | N |
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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
Component | Name: SARS-CoV-2 spike glycoprotein bound to Fab 2-4 / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES | ||||||||||||
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Molecular weight | Value: 515.96 kDa/nm / Experimental value: NO | ||||||||||||
Source (natural) |
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Buffer solution | pH: 5.5 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 266 K |
-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 / Nominal magnification: 81000 X / Cs: 2.7 mm |
Image recording | Electron dose: 51.3 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3576 |
-Processing
Software | Name: UCSF ChimeraX / Version: 0.93/v8 / Classification: model building / URL: https://www.rbvi.ucsf.edu/chimerax/ / Os: Windows / Type: package |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3D reconstruction | Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 83927 / Symmetry type: POINT |