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Yorodumi- PDB-5any: Electron cryo-microscopy of chikungunya virus in complex with neu... -
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-Basic information
Entry | Database: PDB / ID: 5any | ||||||
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Title | Electron cryo-microscopy of chikungunya virus in complex with neutralizing antibody Fab CHK265 | ||||||
Components |
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Keywords | VIRUS / CHIKUNGUNYA VIRUS / NEUTRALIZING ANTIBODY FAB | ||||||
Function / homology | Function and homology information T=4 icosahedral viral capsid / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / structural molecule activity / virion attachment to host cell / host cell plasma membrane / virion membrane / proteolysis ...T=4 icosahedral viral capsid / host cell cytoplasm / symbiont entry into host cell / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / structural molecule activity / virion attachment to host cell / host cell plasma membrane / virion membrane / proteolysis / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | CHIKUNGUNYA VIRUS MUS MUSCULUS (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 16.9 Å | ||||||
Authors | Fox, J.M. / Long, F. / Edeling, M.A. / Lin, H. / Duijl-Richter, M. / Fong, R.H. / Kahle, K.M. / Smit, J.M. / Jin, J. / Simmons, G. ...Fox, J.M. / Long, F. / Edeling, M.A. / Lin, H. / Duijl-Richter, M. / Fong, R.H. / Kahle, K.M. / Smit, J.M. / Jin, J. / Simmons, G. / Doranz, B.J. / Crowe, J.E. / Fremont, D.H. / Rossmann, M.G. / Diamond, M.S. | ||||||
Citation | Journal: Cell / Year: 2015 Title: Broadly Neutralizing Alphavirus Antibodies Bind an Epitope on E2 and Inhibit Entry and Egress. Authors: Julie M Fox / Feng Long / Melissa A Edeling / Hueylie Lin / Mareike K S van Duijl-Richter / Rachel H Fong / Kristen M Kahle / Jolanda M Smit / Jing Jin / Graham Simmons / Benjamin J Doranz / ...Authors: Julie M Fox / Feng Long / Melissa A Edeling / Hueylie Lin / Mareike K S van Duijl-Richter / Rachel H Fong / Kristen M Kahle / Jolanda M Smit / Jing Jin / Graham Simmons / Benjamin J Doranz / James E Crowe / Daved H Fremont / Michael G Rossmann / Michael S Diamond / Abstract: We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of ...We screened a panel of mouse and human monoclonal antibodies (MAbs) against chikungunya virus and identified several with inhibitory activity against multiple alphaviruses. Passive transfer of broadly neutralizing MAbs protected mice against infection by chikungunya, Mayaro, and O'nyong'nyong alphaviruses. Using alanine-scanning mutagenesis, loss-of-function recombinant proteins and viruses, and multiple functional assays, we determined that broadly neutralizing MAbs block multiple steps in the viral lifecycle, including entry and egress, and bind to a conserved epitope on the B domain of the E2 glycoprotein. A 16 Å resolution cryo-electron microscopy structure of a Fab fragment bound to CHIKV E2 B domain provided an explanation for its neutralizing activity. Binding to the B domain was associated with repositioning of the A domain of E2 that enabled cross-linking of neighboring spikes. Our results suggest that B domain antigenic determinants could be targeted for vaccine or antibody therapeutic development against multiple alphaviruses of global concern. | ||||||
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 | 5any.cif.gz | 821.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5any.ent.gz | 672.1 KB | Display | PDB format |
PDBx/mmJSON format | 5any.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/an/5any ftp://data.pdbj.org/pub/pdb/validation_reports/an/5any | HTTPS FTP |
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-Related structure data
Related structure data | 3144MC 5anx M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 48776.719 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) CHIKUNGUNYA VIRUS / Production host: DROSOPHILA MELANOGASTER (fruit fly) / References: UniProt: Q1H8W5 #2: Protein | Mass: 39907.066 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) CHIKUNGUNYA VIRUS / Production host: DROSOPHILA MELANOGASTER (fruit fly) / References: UniProt: Q1H8W5 #3: Antibody | Mass: 23743.719 Da / Num. of mol.: 4 / Fragment: HEAVY CHAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) MUS MUSCULUS (house mouse) / Cell line: HYBRIDOMA / Production host: MUS MUSCULUS (house mouse) #4: Antibody | Mass: 23177.713 Da / Num. of mol.: 4 / Fragment: LIGHT CHAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) MUS MUSCULUS (house mouse) / Cell line: HYBRIDOMA / Production host: MUS MUSCULUS (house mouse) |
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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: chikungunya virus in complex with neutralizing antibody Fab CHK265Chikungunya Type: COMPLEX |
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Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: HOLEY CARBON |
Vitrification | Instrument: GATAN CRYOPLUNGE 3 / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS / Date: Mar 10, 2015 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 47000 X / Calibrated magnification: 78354 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 22 e/Å2 / Film or detector model: GATAN ULTRASCAN 4000 (4k x 4k) |
Image scans | Num. digital images: 500 |
-Processing
EM software | Name: jspr / Category: 3D reconstruction | ||||||||||||
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CTF correction | Details: EACH PARTICLE | ||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||
3D reconstruction | Method: CROSS-COMMON LINES / Resolution: 16.9 Å / Num. of particles: 5828 Details: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3144. (DEPOSITION ID: 13751) Symmetry type: POINT | ||||||||||||
Refinement | Highest resolution: 16.9 Å | ||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 16.9 Å
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