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Yorodumi- PDB-7sfv: CryoEM structure of Venezuelan Equine Encephalitis virus (VEEV) T... -
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-Basic information
Entry | Database: PDB / ID: 7sfv | ||||||
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Title | CryoEM structure of Venezuelan Equine Encephalitis virus (VEEV) TC-83 strain VLP in complex with Fab hVEEV-63 | ||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / VLP / VEEV / viral protein / fab / VIRUS-IMMUNE SYSTEM complex | ||||||
Function / homology | : Function and homology information | ||||||
Biological species | Venezuelan equine encephalitis virus Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 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 | 7sfv.cif.gz | 934.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7sfv.ent.gz | 773.9 KB | Display | PDB format |
PDBx/mmJSON format | 7sfv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7sfv_validation.pdf.gz | 715.7 KB | Display | wwPDB validaton report |
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Full document | 7sfv_full_validation.pdf.gz | 785.3 KB | Display | |
Data in XML | 7sfv_validation.xml.gz | 125.5 KB | Display | |
Data in CIF | 7sfv_validation.cif.gz | 208.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sf/7sfv ftp://data.pdbj.org/pub/pdb/validation_reports/sf/7sfv | HTTPS FTP |
-Related structure data
Related structure data | 25103MC 7sfuC 7sfwC 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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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
-Spike glycoprotein ... , 2 types, 8 molecules ADGJBEHK
#1: Protein | Mass: 47699.820 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: 46556.094 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: 23197.908 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: 22480.836 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: 17781.336 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: RECOMBINANT |
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Molecular weight | Units: MEGADALTONS / Experimental value: NO |
Source (natural) | Organism: Venezuelan equine encephalitis virus (strain TC-83) |
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
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 19000 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 17500 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL |