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Open data
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Basic information
| Entry | Database: PDB / ID: 9hbk | ||||||
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| Title | Structure of A16/G9 in complex with A56/K2 (vaccinia virus) | ||||||
Components |
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Keywords | VIRAL PROTEIN / poxvirus / viral fusion / vaccinia virus / mpox virus | ||||||
| Function / homology | Function and homology informationmembrane fusion involved in viral entry into host cell / host cell membrane / serine-type endopeptidase inhibitor activity / DNA-templated transcription termination / helicase activity / hydrolase activity / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / host cell plasma membrane ...membrane fusion involved in viral entry into host cell / host cell membrane / serine-type endopeptidase inhibitor activity / DNA-templated transcription termination / helicase activity / hydrolase activity / fusion of virus membrane with host plasma membrane / viral envelope / symbiont entry into host cell / host cell plasma membrane / virion membrane / extracellular space / DNA binding / ATP binding / membrane Similarity search - Function | ||||||
| Biological species | Vaccinia virus Western Reserve | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
Authors | Vernuccio, R. / Meola, A. / Guardado-Calvo, P. | ||||||
| Funding support | France, 1items
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Citation | Journal: Cell / Year: 2025Title: Structural basis of poxvirus fusion regulation and anti-A16/G9 antibody-mediated neutralization and protection. Authors: Annalisa Meola / Riccardo Vernuccio / Leandro Battini / Guillermo Albericio / Pilar Delgado / Rebecca Bamford / Laura Pokorny / Manon Broutin / Alejandro Martínez León / Sébastien Gallien ...Authors: Annalisa Meola / Riccardo Vernuccio / Leandro Battini / Guillermo Albericio / Pilar Delgado / Rebecca Bamford / Laura Pokorny / Manon Broutin / Alejandro Martínez León / Sébastien Gallien / María Gil / María A Noriega / Florence Guivel-Benhassine / Françoise Porrot / Jeanne Postal / Julian Buchrieser / Mathieu Hubert / Ahmed Haouz / Pierre Lafaye / Mariano Esteban / Jochen S Hub / Matthieu Mahévas / Pascal Chappert / Jason Mercer / Juan Garcia-Arriaza / Olivier Schwartz / Pablo Guardado-Calvo / ![]() Abstract: Monkeypox virus (MPXV) is a poxvirus endemic to Central and West Africa with high epidemic potential. Poxviruses enter host cells via a conserved entry-fusion complex (EFC), which mediates viral ...Monkeypox virus (MPXV) is a poxvirus endemic to Central and West Africa with high epidemic potential. Poxviruses enter host cells via a conserved entry-fusion complex (EFC), which mediates viral fusion to the cell membrane. The EFC is a promising therapeutic target, but the absence of structural data has limited the development of fusion-inhibiting treatments. Here, we investigated A16/G9, a subcomplex of the EFC that controls fusion timing. Using cryo-electron microscopy, we showed how A16/G9 interacts with A56/K2, a viral fusion suppressor that prevents superinfection. Immunization with A16/G9 elicited a protective immune response in mice. Using X-ray crystallography, we characterized two neutralizing antibodies and engineered a chimeric antibody that cross-neutralizes several poxviruses more efficiently than 7D11, the most potent antibody targeting the EFC described to date. These findings highlight the potential of A16/G9 as a candidate for subunit vaccines and identify regions of the EFC as targets for antiviral development. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9hbk.cif.gz | 276.4 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9hbk.ent.gz | 173.3 KB | Display | PDB format |
| PDBx/mmJSON format | 9hbk.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 9hbk_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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| Full document | 9hbk_full_validation.pdf.gz | 1.4 MB | Display | |
| Data in XML | 9hbk_validation.xml.gz | 42.4 KB | Display | |
| Data in CIF | 9hbk_validation.cif.gz | 63.6 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hb/9hbk ftp://data.pdbj.org/pub/pdb/validation_reports/hb/9hbk | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 52019MC ![]() 9hl2C ![]() 9hlsC ![]() 9hngC ![]() 9hpaC ![]() 9r09C ![]() 9r0bC ![]() 9r0jC ![]() 9rdhC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein , 4 types, 4 molecules ABCD
| #1: Protein | Mass: 39110.977 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vaccinia virus Western Reserve / Gene: OPG143, VACWR136, A16L / Cell line (production host): S2 cells / Production host: ![]() |
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| #2: Protein | Mass: 35601.871 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vaccinia virus Western Reserve / Gene: OPG094, VACWR087, G9R / Cell line (production host): S2 cells / Production host: ![]() |
| #3: Protein | Mass: 46738.910 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vaccinia virus Western Reserve / Gene: OPG040, K2L, SPI-3, VACWR033 / Production host: ![]() |
| #4: Protein | Mass: 15592.021 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Vaccinia virus Western Reserve / Gene: OPG185, HA, VACWR181, A56R / Cell line (production host): S2 cells / Production host: ![]() |
-Sugars , 4 types, 4 molecules 
| #5: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
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| #6: Polysaccharide | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose |
| #7: 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 |
| #8: Sugar | ChemComp-NAG / |
-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Quaternary complex of vaccinia virus A16, G9, K2, and the Ig domain of K2 Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.155 MDa / Experimental value: NO |
| Source (natural) | Organism: Vaccinia virus / Strain: Western reserve |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 7.5 / Details: PBS |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: concentration = 2 uM |
| Specimen support | Grid material: GOLD / Grid type: Quantifoil |
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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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: 3000 nm / Nominal defocus min: 750 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm |
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
| Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Version: 1.21.2_5419 / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 228433 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
| Displacement parameters | Biso mean: 70.28 Å2 | ||||||||||||||||||||||||
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Vaccinia virus Western Reserve
France, 1items
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FIELD EMISSION GUN