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Yorodumi- PDB-7r40: Structure of the SARS-CoV-2 spike glycoprotein in complex with th... -
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-Basic information
Entry | Database: PDB / ID: 7r40 | ||||||||||||
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Title | Structure of the SARS-CoV-2 spike glycoprotein in complex with the 87G7 antibody Fab fragment | ||||||||||||
Components |
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Keywords | VIRAL PROTEIN / Coronavirus / Spike / Antibody / 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 / membrane fusion / Attachment and Entry / 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 / 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: 2.9 Å | ||||||||||||
Authors | Hurdiss, D.L. | ||||||||||||
Funding support | European Union, Germany, 3items
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Citation | Journal: Sci Immunol / Year: 2022 Title: An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern. Authors: Wenjuan Du / Daniel L Hurdiss / Dubravka Drabek / Anna Z Mykytyn / Franziska K Kaiser / Mariana González-Hernández / Diego Muñoz-Santos / Mart M Lamers / Rien van Haperen / Wentao Li / ...Authors: Wenjuan Du / Daniel L Hurdiss / Dubravka Drabek / Anna Z Mykytyn / Franziska K Kaiser / Mariana González-Hernández / Diego Muñoz-Santos / Mart M Lamers / Rien van Haperen / Wentao Li / Ieva Drulyte / Chunyan Wang / Isabel Sola / Federico Armando / Georg Beythien / Malgorzata Ciurkiewicz / Wolfgang Baumgärtner / Kate Guilfoyle / Tony Smits / Joline van der Lee / Frank J M van Kuppeveld / Geert van Amerongen / Bart L Haagmans / Luis Enjuanes / Albert D M E Osterhaus / Frank Grosveld / Berend-Jan Bosch / Abstract: 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 ...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. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7r40.cif.gz | 703.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7r40.ent.gz | 562.1 KB | Display | PDB format |
PDBx/mmJSON format | 7r40.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7r40_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 7r40_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 7r40_validation.xml.gz | 110.3 KB | Display | |
Data in CIF | 7r40_validation.cif.gz | 165.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r4/7r40 ftp://data.pdbj.org/pub/pdb/validation_reports/r4/7r40 | HTTPS FTP |
-Related structure data
Related structure data | 14250MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 141048.734 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 / Cell line (production host): HEK-293T / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 #2: Antibody | Mass: 23550.207 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK-293T / Production host: Homo sapiens (human) #3: Antibody | Mass: 23915.703 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK-293T / Production host: Homo sapiens (human) #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: Sugar | ChemComp-NAG / 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 |
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Molecular weight | Value: 0.5 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Conc.: 4 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 51.5 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 3831 Details: 1331 images collected from grid 1 (0.02% FOM) and 2500 images collected from grid 2 (0% FOM) |
EM imaging optics | Energyfilter name: TFS Selectris X / Energyfilter slit width: 10 eV |
Image scans | Sampling size: 14 µm / Width: 4096 / Height: 4096 |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 934811 Details: 313636 particles were picked from 1331 images from 0.02% FOM dataset and 621175 particles were picked from 2500 images without FOM. | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 133550 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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Refine LS restraints |
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