+Open data
-Basic information
Entry | Database: PDB / ID: 5yhq | ||||||
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Title | Cryo-EM Structure of CVA6 VLP | ||||||
Components |
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Keywords | VIRUS LIKE PARTICLE / Coxsackievirus A6 / virus-like particle / cryo-EM / near-atomic resolution structure / epitope | ||||||
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 / channel activity ...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 / channel activity / nucleoside-triphosphate phosphatase / monoatomic ion transmembrane transport / RNA helicase activity / induction by virus of host autophagy / symbiont entry into host cell / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | ||||||
Biological species | Coxsackievirus A6 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Chen, J. / Zhang, C. / Huang, Z. / Cong, Y. | ||||||
Citation | Journal: J Virol / Year: 2018 Title: A 3.0-Angstrom Resolution Cryo-Electron Microscopy Structure and Antigenic Sites of Coxsackievirus A6-Like Particles. Authors: Jinhuan Chen / Chao Zhang / Yu Zhou / Xiang Zhang / Chaoyun Shen / Xiaohua Ye / Wen Jiang / Zhong Huang / Yao Cong / Abstract: Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved ...Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). The structure of the CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the first cryo-electron microscopy (cryo-EM) structure of the CVA6 VLP at 3.0-Å resolution. The CVA6 VLP exhibits the characteristic features of enteroviruses but presents an open channel at the 2-fold axis and an empty, collapsed VP1 pocket, which is broadly similar to the structures of the enterovirus 71 (EV71) VLP and coxsackievirus A16 (CVA16) 135S expanded particle, indicating that the CVA6 VLP is in an expanded conformation. Structural comparisons reveal that two common salt bridges within protomers are maintained in the CVA6 VLP and other viruses of the genus, implying that these salt bridges may play a critical role in enteroviral protomer assembly. However, there are apparent structural differences among the CVA6 VLP, EV71 VLP, and CVA16 135S particle in the surface-exposed loops and C termini of subunit proteins, which are often antigenic sites for enteroviruses. By immunological assays, we identified two CVA6-specific linear B-cell epitopes (designated P42 and P59) located at the GH loop and the C-terminal region of VP1, respectively, in agreement with the structure-based prediction of antigenic sites. Our findings elucidate the structural basis and important antigenic sites of the CVA6 VLP as a strong vaccine candidate and also provide insight into enteroviral protomer assembly. Coxsackievirus A6 (CVA6) is becoming one of the major pathogens causing hand, foot, and mouth disease (HFMD), leading to significant morbidity and mortality in children and adults. However, no vaccine is currently available to prevent CVA6 infection. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 are a promising CVA6 vaccine candidate. Here, we present a 3.0-Å structure of the CVA6 VLP determined by cryo-electron microscopy. The overall architecture of the CVA6 VLP is similar to those of the expanded structures of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but careful structural comparisons reveal significant differences in the surface-exposed loops and C termini of each capsid protein of these particles. In addition, we identified two CVA6-specific linear B-cell epitopes and mapped them to the GH loop and the C-terminal region of VP1, respectively. Collectively, our findings provide a structural basis and important antigenic information for CVA6 VLP vaccine 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 | 5yhq.cif.gz | 138.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5yhq.ent.gz | 105.3 KB | Display | PDB format |
PDBx/mmJSON format | 5yhq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5yhq_validation.pdf.gz | 1022.2 KB | Display | wwPDB validaton report |
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Full document | 5yhq_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 5yhq_validation.xml.gz | 27.8 KB | Display | |
Data in CIF | 5yhq_validation.cif.gz | 39.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yh/5yhq ftp://data.pdbj.org/pub/pdb/validation_reports/yh/5yhq | HTTPS FTP |
-Related structure data
Related structure data | 6829MC 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: 33644.395 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus A6 / Gene: VP1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9YLP0 |
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#2: Protein | Mass: 26375.834 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 326-565 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus A6 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q6JKS2 |
#3: Protein | Mass: 35351.426 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 1-325 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Coxsackievirus A6 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q6JKS2 |
-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: Coxsackievirus A6 / Type: VIRUS / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Coxsackievirus A6 |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Details of virus | Empty: YES / Enveloped: NO / Isolate: OTHER / Type: VIRUS-LIKE PARTICLE |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
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 |
Image recording | Electron dose: 42 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.10.1_2155: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 11596 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Highest resolution: 3 Å | ||||||||||||||||||||||||
Refine LS restraints |
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