+Open data
-Basic information
Entry | Database: PDB / ID: 6ad0 | ||||||||||||||||||||||||||||||
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Title | The structure of CVA10 mature virion in complex with Fab 2G8 | ||||||||||||||||||||||||||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / CVA10 / immune complex / neutralizing antibody / VIRUS / VIRUS-IMMUNE SYSTEM complex | ||||||||||||||||||||||||||||||
Function / homology | Function and homology information symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / host cell cytoplasm / RNA helicase activity / induction by virus of host autophagy / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding / cytoplasm Similarity search - Function | ||||||||||||||||||||||||||||||
Biological species | Mus musculus (house mouse) Coxsackievirus A10 | ||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||||||||||||||||||||
Authors | Zhu, R. / Zheng, Q.B. / Xu, L.F. / Cui, Y.X. / Li, S.W. / Yan, X.D. / Zhou, Z.H. / Cheng, T. | ||||||||||||||||||||||||||||||
Funding support | China, United States, 9items
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Citation | Journal: Sci Adv / Year: 2018 Title: Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10. Authors: Rui Zhu / Longfa Xu / Qingbing Zheng / Yanxiang Cui / Shaowei Li / Maozhou He / Zhichao Yin / Dongxiao Liu / Shuxuan Li / Zizhen Li / Zhenqin Chen / Hai Yu / Yuqiong Que / Che Liu / Zhibo ...Authors: Rui Zhu / Longfa Xu / Qingbing Zheng / Yanxiang Cui / Shaowei Li / Maozhou He / Zhichao Yin / Dongxiao Liu / Shuxuan Li / Zizhen Li / Zhenqin Chen / Hai Yu / Yuqiong Que / Che Liu / Zhibo Kong / Jun Zhang / Timothy S Baker / Xiaodong Yan / Z Hong Zhou / Tong Cheng / Ningshao Xia / Abstract: Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has ...Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has made therapeutic antibody identification a public health priority. By targeting a local isolate, CVA10-FJ-01, we obtained a potent antibody, 2G8, against all three capsid forms of CVA10. We show that 2G8 exhibited both 100% preventive and 100% therapeutic efficacy against CVA10 infection in mice. Comparisons of the near-atomic cryo-electron microscopy structures of the three forms of CVA10 capsid and their complexes with 2G8 Fab reveal that a single Fab binds a border region across the three capsid proteins (VP1 to VP3) and explain 2G8's remarkable cross-reactivities against all three capsid forms. The atomic structures of this first neutralizing antibody of CVA10 should inform strategies for designing vaccines and therapeutics against CVA10 infections. | ||||||||||||||||||||||||||||||
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 | 6ad0.cif.gz | 193.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ad0.ent.gz | 151.8 KB | Display | PDB format |
PDBx/mmJSON format | 6ad0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ad/6ad0 ftp://data.pdbj.org/pub/pdb/validation_reports/ad/6ad0 | HTTPS FTP |
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-Related structure data
Related structure data | 9604MC 9600C 9601C 9602C 9603C 9605C 9606C 6acuC 6acwC 6acyC 6aczC 6ad1C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
-Protein , 4 types, 4 molecules ABCD
#3: Protein | Mass: 33159.230 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A10 / References: UniProt: A0A1V0FT21 |
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#4: Protein | Mass: 27808.133 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A10 / References: UniProt: A0A1V0FT21 |
#5: Protein | Mass: 26129.588 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A10 / References: UniProt: A0A1V0FT21 |
#6: Protein | Mass: 7464.104 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A10 / References: UniProt: Q75Q92, UniProt: A0A1V0FT21*PLUS |
-Antibody , 2 types, 2 molecules LH
#1: Antibody | Mass: 12391.881 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
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#2: Antibody | Mass: 13149.508 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse) |
-Non-polymers , 1 types, 1 molecules
#7: Chemical | ChemComp-SPH / |
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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: CVA10 mature virion in complex with Fab 2G8 / Type: VIRUS / Entity ID: #1-#6 |
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Source (natural) | Organism: Coxsackievirus A10 |
Details of virus | Empty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Tecnai F30 / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI F30 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 25 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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Symmetry | Point symmetry: I (icosahedral) |
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 36555 / Symmetry type: POINT |