+Open data
-Basic information
Entry | Database: PDB / ID: 5ywp | ||||||
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Title | JEV-2H4 Fab complex | ||||||
Components |
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Keywords | IMMUNE SYSTEM / Flaviviruses / Viral encephalitis / neutralizing monoclonal antibodies / structural analysis / viral entry | ||||||
Function / homology | Function and homology information symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell surface / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / serine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | Japanese encephalitis virus Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.6 Å | ||||||
Authors | Qiu, X.D. / Lei, Y.F. / Yang, P. / Gao, Q. / WANG, N. / Cao, L. / Yuan, S. / Wang, X.X. / Xu, Z.K. / Rao, Z.H. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Microbiol / Year: 2018 Title: Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies. Authors: Xiaodi Qiu / Yingfeng Lei / Pan Yang / Qiang Gao / Nan Wang / Lei Cao / Shuai Yuan / Xiaofang Huang / Yongqiang Deng / Wenyu Ma / Tianbing Ding / Fanglin Zhang / Xingan Wu / Junjie Hu / Shan- ...Authors: Xiaodi Qiu / Yingfeng Lei / Pan Yang / Qiang Gao / Nan Wang / Lei Cao / Shuai Yuan / Xiaofang Huang / Yongqiang Deng / Wenyu Ma / Tianbing Ding / Fanglin Zhang / Xingan Wu / Junjie Hu / Shan-Lu Liu / Chengfeng Qin / Xiangxi Wang / Zhikai Xu / Zihe Rao / Abstract: Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . JEV is the leading causative agent of ...Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized . JEV is the leading causative agent of encephalitis, and is responsible for thousands of deaths each year in Asia. Humoral immunity is essential for protecting against flavivirus infections and passive immunization has been demonstrated to be effective in curing disease. Here, we demonstrate that JEV-specific monoclonal antibodies, 2F2 and 2H4, block attachment of the virus to its receptor and also prevent fusion of the virus. Neutralization of JEV by these antibodies is exceptionally potent and confers clear therapeutic benefit in mouse models. A single 20 μg dose of these antibodies resulted in 100% survival and complete clearance of JEV from the brains of mice. The 4.7 Å and 4.6 Å resolution cryo-electron microscopy structures of JEV-2F2-Fab and JEV-2H4-Fab complexes, together with the crystal structure of 2H4 Fab and our recent near-atomic structure of JEV , unveil the nature and location of epitopes targeted by the antibodies. Both 2F2 and 2H4 Fabs bind quaternary epitopes that span across three adjacent envelope proteins. Our results provide a structural and molecular basis for the application of 2F2 and 2H4 to treat JEV infection. | ||||||
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 | 5ywp.cif.gz | 449.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ywp.ent.gz | 382.9 KB | Display | PDB format |
PDBx/mmJSON format | 5ywp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5ywp_validation.pdf.gz | 991.3 KB | Display | wwPDB validaton report |
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Full document | 5ywp_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5ywp_validation.xml.gz | 92.5 KB | Display | |
Data in CIF | 5ywp_validation.cif.gz | 138 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yw/5ywp ftp://data.pdbj.org/pub/pdb/validation_reports/yw/5ywp | HTTPS FTP |
-Related structure data
Related structure data | 6855MUC 6854C 5ywfC 5ywoC M: map data used to model this data U: unfit; in different coordinate system*YM C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 53508.684 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Japanese encephalitis virus / References: UniProt: P32886*PLUS #2: Protein | Mass: 8250.488 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Japanese encephalitis virus / References: UniProt: P27395*PLUS #3: Antibody | Mass: 23840.303 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) #4: Antibody | Mass: 23337.305 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) 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: JEV E protein with its mouse antibody H / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Japanese encephalitis virus / Strain: P3 |
Source (recombinant) | Organism: Chlorocebus aethiops (grivet) |
Buffer solution | pH: 7.4 / Details: PBS |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. |
Vitrification | Cryogen name: ETHANE |
-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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Calibrated defocus min: 1000 nm / Calibrated defocus max: 3000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Image recording | Average exposure time: 8 sec. / Electron dose: 25 e/Å2 / Detector mode: OTHER / Film or detector model: FEI FALCON III (4k x 4k) / Num. of real images: 2500 |
Image scans | Width: 4000 / Height: 4000 |
-Processing
Software | Name: PHENIX / Version: 1.10.1_2155: / 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: 26229 | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26229 / Num. of class averages: 50 / Symmetry type: POINT | ||||||||||||||||||||||||||||
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