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Yorodumi- PDB-7sfw: CryoEM structure of Venezuelan Equine Encephalitis virus (VEEV) T... -
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-Basic information
Entry | Database: PDB / ID: 7sfw | ||||||
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Title | CryoEM structure of Venezuelan Equine Encephalitis virus (VEEV) TC-83 strain VLP in complex with Fab hVEEV-63 (focus refine of the asymmetric unit) | ||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / VLP / VEEV / viral protein / fab / VIRUS-IMMUNE SYSTEM complex | ||||||
Function / homology | Function and homology information togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host gene expression / symbiont-mediated suppression of host toll-like receptor signaling pathway / clathrin-dependent endocytosis of virus by host cell / host cell cytoplasm / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus ...togavirin / T=4 icosahedral viral capsid / symbiont-mediated suppression of host gene expression / symbiont-mediated suppression of host toll-like receptor signaling pathway / clathrin-dependent endocytosis of virus by host cell / host cell cytoplasm / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / RNA binding / membrane Similarity search - Function | ||||||
Biological species | Venezuelan equine encephalitis virus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Binshtein, E. / Crowe, J.E. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Exp Med / Year: 2022 Title: Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge. Authors: Natasha M Kafai / Lauren E Williamson / Elad Binshtein / Soila Sukupolvi-Petty / Christina L Gardner / Jaclyn Liu / Samantha Mackin / Arthur S Kim / Nurgun Kose / Robert H Carnahan / Ana ...Authors: Natasha M Kafai / Lauren E Williamson / Elad Binshtein / Soila Sukupolvi-Petty / Christina L Gardner / Jaclyn Liu / Samantha Mackin / Arthur S Kim / Nurgun Kose / Robert H Carnahan / Ana Jung / Lindsay Droit / Douglas S Reed / Scott A Handley / William B Klimstra / James E Crowe / Michael S Diamond / Abstract: Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing ...Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development. | ||||||
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 | 7sfw.cif.gz | 861.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sfw.ent.gz | 697.9 KB | Display | PDB format |
PDBx/mmJSON format | 7sfw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7sfw_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7sfw_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7sfw_validation.xml.gz | 139.2 KB | Display | |
Data in CIF | 7sfw_validation.cif.gz | 211.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sf/7sfw ftp://data.pdbj.org/pub/pdb/validation_reports/sf/7sfw | HTTPS FTP |
-Related structure data
Related structure data | 25104MC 7sfuC 7sfvC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Spike glycoprotein ... , 2 types, 8 molecules ADGJBEHK
#1: Protein | Mass: 47952.066 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Venezuelan equine encephalitis virus (strain TC-83) Strain: TC-83 / Production host: Homo sapiens (human) / References: UniProt: P05674 #2: Protein | Mass: 47113.746 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Venezuelan equine encephalitis virus (strain TC-83) Strain: TC-83 / Production host: Homo sapiens (human) / References: UniProt: P05674 |
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-Antibody , 2 types, 8 molecules MOQSNPRT
#4: Antibody | Mass: 13403.909 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) #5: Antibody | Mass: 11515.588 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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-Protein / Sugars , 2 types, 16 molecules CFIL
#3: Protein | Mass: 30995.879 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Venezuelan equine encephalitis virus (strain TC-83) Strain: TC-83 / Production host: Homo sapiens (human) / References: UniProt: P05674, togavirin #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
Component | Name: Venezuelan equine encephalitis virus (strain TC-83) / Type: VIRUS / Entity ID: #1-#5 / Source: MULTIPLE SOURCES | ||||||||||||
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Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||
Source (natural) |
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Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||
Details of virus | Empty: YES / Enveloped: YES / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE | ||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 293.15 K / Details: Lacey Carbon |
-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: OTHER |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 75000 X / Nominal defocus max: 1600 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 8.14 sec. / Electron dose: 40.05 e/Å2 / Detector mode: COUNTING / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 10586 |
Image scans | Sampling size: 14 µm |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 19000 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 405000 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 60.03 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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