[English] 日本語
Yorodumi
- PDB-5yhq: Cryo-EM Structure of CVA6 VLP -

+
Open data


ID or keywords:

Loading...

no data

-
Basic information

Entry
Database: PDB / ID: 5yhq
TitleCryo-EM Structure of CVA6 VLP
Components
  • Capsid protein VP1
  • Capsid protein VP3
  • capsid protein VP0
KeywordsVIRUS LIKE PARTICLE / Coxsackievirus A6 / virus-like particle / cryo-EM / near-atomic resolution structure / epitope
Function / homologyPeptidase C3A/C3B, picornaviral / picornavirus capsid protein / Protein of unknown function DUF3724, picornavirus / Poliovirus 3A protein-like / Helicase, superfamily 3, single-stranded RNA virus / Peptidase S1, PA clan / RNA-directed RNA polymerase, catalytic domain / AAA+ ATPase domain / Picornavirus coat protein VP4 / Picornavirus 2B protein ...Peptidase C3A/C3B, picornaviral / picornavirus capsid protein / Protein of unknown function DUF3724, picornavirus / Poliovirus 3A protein-like / Helicase, superfamily 3, single-stranded RNA virus / Peptidase S1, PA clan / RNA-directed RNA polymerase, catalytic domain / AAA+ ATPase domain / Picornavirus coat protein VP4 / Picornavirus 2B protein / Picornavirus capsid / RNA-directed RNA polymerase, C-terminal domain / Helicase, superfamily 3, single-stranded DNA/RNA virus / Peptidase C3, picornavirus core protein 2A / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / Poliovirus core protein 3a, soluble domain / P-loop containing nucleoside triphosphate hydrolase / Picornavirus core protein 2A / 3C cysteine protease (picornain 3C) / RNA dependent RNA polymerase / Superfamily 3 helicase of positive ssRNA viruses domain profile. / RdRp of positive ssRNA viruses catalytic domain profile. / Protein of unknown function (DUF3724) / Poliovirus 3A protein like / Picornavirus coat protein (VP4) / Picornavirus 2B protein / RNA helicase / T=pseudo3 icosahedral viral capsid / picornain 2A / pore-mediated entry of viral genome into host cell / suppression by virus of host mRNA export from nucleus / suppression by virus of host RIG-I activity / picornain 3C / endocytosis involved in viral entry into host cell / RNA-protein covalent cross-linking / host cell cytoplasmic vesicle membrane / RNA helicase activity / pore formation by virus in membrane of host cell / integral to membrane of host cell / nucleoside-triphosphatase / viral capsid / RNA-directed RNA polymerase / ion channel activity / induction by virus of host autophagy / suppression by virus of host gene expression / protein complex oligomerization / viral RNA genome replication / RNA-directed 5'-3' RNA polymerase activity / cysteine-type endopeptidase activity / virion attachment to host cell / structural molecule activity / transcription, DNA-templated / RNA binding / membrane / ATP binding / Genome polyprotein / Capsid protein VP1
Function and homology information
Specimen sourceCoxsackievirus A6
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 3 Å resolution
AuthorsChen, J. / Zhang, C. / Huang, Z. / Cong, Y.
CitationJournal: 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.
Validation Report
SummaryFull reportAbout validation report
DateDeposition: Sep 29, 2017 / Release: Oct 25, 2017
RevisionDateData content typeGroupCategoryItemProviderType
1.0Oct 25, 2017Structure modelrepositoryInitial release
1.1Nov 1, 2017Structure modelDerived calculationspdbx_struct_oper_list_pdbx_struct_oper_list.matrix[1][1] / _pdbx_struct_oper_list.matrix[1][2] / _pdbx_struct_oper_list.matrix[1][3] / _pdbx_struct_oper_list.matrix[2][1] / _pdbx_struct_oper_list.matrix[2][2] / _pdbx_struct_oper_list.matrix[2][3] / _pdbx_struct_oper_list.matrix[3][1] / _pdbx_struct_oper_list.matrix[3][2] / _pdbx_struct_oper_list.matrix[3][3]

-
Structure visualization

Movie
  • Biological unit as complete icosahedral assembly
  • Imaged by Jmol
  • Download
  • Biological unit as icosahedral pentamer
  • Imaged by Jmol
  • Download
  • Biological unit as icosahedral 23 hexamer
  • Imaged by Jmol
  • Download
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-6829
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-6829
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Capsid protein VP1
C: Capsid protein VP3
B: capsid protein VP0


Theoretical massNumber of molelcules
Total (without water)95,3723
Polyers95,3723
Non-polymers00
Water0
1
A: Capsid protein VP1
C: Capsid protein VP3
B: capsid protein VP0
x 60


Theoretical massNumber of molelcules
Total (without water)5,722,299180
Polyers5,722,299180
Non-polymers00
Water0
TypeNameSymmetry operationNumber
point symmetry operation60
2


  • idetical with deposited unit in distinct coordinate
  • icosahedral asymmetric unit
TypeNameSymmetry operationNumber
point symmetry operation1
3
A: Capsid protein VP1
C: Capsid protein VP3
B: capsid protein VP0
x 5


  • icosahedral pentamer
  • 477 kDa, 15 polymers
Theoretical massNumber of molelcules
Total (without water)476,85815
Polyers476,85815
Non-polymers00
Water0
TypeNameSymmetry operationNumber
point symmetry operation5
4
A: Capsid protein VP1
C: Capsid protein VP3
B: capsid protein VP0
x 6


  • icosahedral 23 hexamer
  • 572 kDa, 18 polymers
Theoretical massNumber of molelcules
Total (without water)572,23018
Polyers572,23018
Non-polymers00
Water0
TypeNameSymmetry operationNumber
point symmetry operation6
5


  • idetical with deposited unit in distinct coordinate
  • icosahedral asymmetric unit, std point frame
TypeNameSymmetry operationNumber
transform to point frame1

-
Components

#1: Protein/peptide Capsid protein VP1 /


Mass: 33644.395 Da / Num. of mol.: 1 / Source: (gene. exp.) Coxsackievirus A6 / Gene: VP1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9YLP0
#2: Protein/peptide Capsid protein VP3 /


Mass: 26375.834 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 326-565 / Source: (gene. exp.) Coxsackievirus A6 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q6JKS2
#3: Protein/peptide capsid protein VP0 /


Mass: 35351.426 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 1-325 / Source: (gene. exp.) Coxsackievirus A6 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q6JKS2

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / Reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Coxsackievirus A6 / Type: VIRUS / Entity ID: 1, 2, 3 / Source: RECOMBINANT
Source (natural)Organism: Coxsackievirus A6
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Details of virusEmpty: YES / Enveloped: NO / Virus isolate: OTHER / Virus type: VIRUS-LIKE PARTICLE
Buffer solutionpH: 7.2
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyMicroscope model: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 42 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.10.1_2155: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 11596 / Symmetry type: POINT
Least-squares processHighest resolution: 3 Å
Refine LS restraints
Refine IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0095490
ELECTRON MICROSCOPYf_angle_d0.8217505
ELECTRON MICROSCOPYf_dihedral_angle_d11.6774343
ELECTRON MICROSCOPYf_chiral_restr0.056830
ELECTRON MICROSCOPYf_plane_restr0.007972

+
About Yorodumi

-
News

-
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.

External links: wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

+
Apr 13, 2016. Omokage search got faster

Omokage search got faster

  • The computation time became ~1/2 compared to the previous version by re-optimization of data accession
  • Enjoy "shape similarity" of biomolecules, more!

Related info.: Omokage search

Read more

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.

Related info.: EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more