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- EMDB-6751: Structure of Coxsackievirus A6 (CVA6) virus A-particle -

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Basic information

Entry
Database: EMDB / ID: EMD-6751
TitleStructure of Coxsackievirus A6 (CVA6) virus A-particle
Map dataNone
Sample
  • Virus: Coxsackievirus A6
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
KeywordsCoxsackievirus A6 / A-particle / icosahedral / VIRUS
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 / nucleoside-triphosphate phosphatase ...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 / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport / RNA helicase activity / induction by virus of host autophagy / 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
Protein of unknown function DUF3724, picornavirus / Protein of unknown function (DUF3724) / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A ...Protein of unknown function DUF3724, picornavirus / Protein of unknown function (DUF3724) / Picornavirus coat protein / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Reverse transcriptase/Diguanylate cyclase domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Biological speciesCoxsackievirus A6
Methodsingle particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsZheng QB / He MZ
Funding support China, United States, 6 items
OrganizationGrant numberCountry
National Natural Science Foundation of China31670933 China
National Natural Science Foundation of China81401669 China
National Science and Technology Major Projects for Major New Drugs Innovation and Development2017ZX09101005-005-003 China
National Science and Technology Major Project of Infectious Diseases2017ZX10304402-002-003 China
Natural Science Foundation of Fujian Province2015J05073 China
National Institutes of HealthR37-GM33050 United States
CitationJournal: Nat Commun / Year: 2017
Title: Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody.
Authors: Longfa Xu / Qingbing Zheng / Shaowei Li / Maozhou He / Yangtao Wu / Yongchao Li / Rui Zhu / Hai Yu / Qiyang Hong / Jie Jiang / Zizhen Li / Shuxuan Li / Huan Zhao / Lisheng Yang / Wangheng ...Authors: Longfa Xu / Qingbing Zheng / Shaowei Li / Maozhou He / Yangtao Wu / Yongchao Li / Rui Zhu / Hai Yu / Qiyang Hong / Jie Jiang / Zizhen Li / Shuxuan Li / Huan Zhao / Lisheng Yang / Wangheng Hou / Wei Wang / Xiangzhong Ye / Jun Zhang / Timothy S Baker / Tong Cheng / Z Hong Zhou / Xiaodong Yan / Ningshao Xia /
Abstract: Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the ...Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses. Our near-atomic resolution structure of CVA6 A-particle complexed with a neutralizing antibody maps an immune-dominant neutralizing epitope to the surface loops of VP1. The structure-guided cell-based inhibition studies further demonstrate that these loops could serve as excellent targets for designing anti-CVA6 vaccines.Coxsackievirus A6 (CVA6) causes hand, foot and mouth disease in children. Here the authors present the CVA6 procapsid and A-particle cryo-EM structures and identify an immune-dominant neutralizing epitope, which can be exploited for vaccine development.
History
DepositionJun 12, 2017-
Header (metadata) releaseSep 27, 2017-
Map releaseSep 27, 2017-
UpdateMar 27, 2024-
Current statusMar 27, 2024Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0738
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.0738
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-5xs4
  • Surface level: 0.0738
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-5xs4
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_6751.map.gz / Format: CCP4 / Size: 262.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationNone
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.13 Å/pix.
x 410 pix.
= 462.48 Å
1.13 Å/pix.
x 410 pix.
= 462.48 Å
1.13 Å/pix.
x 410 pix.
= 462.48 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.128 Å
Density
Contour LevelBy AUTHOR: 0.0738 / Movie #1: 0.0738
Minimum - Maximum-0.16141656 - 0.26443833
Average (Standard dev.)0.000914049 (±0.019542186)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions410410410
Spacing410410410
CellA=B=C: 462.48 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.1281.1281.128
M x/y/z410410410
origin x/y/z0.0000.0000.000
length x/y/z462.480462.480462.480
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS410410410
D min/max/mean-0.1610.2640.001

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Supplemental data

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Sample components

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Entire : Coxsackievirus A6

EntireName: Coxsackievirus A6
Components
  • Virus: Coxsackievirus A6
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein
    • Protein or peptide: Genome polyprotein

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Supramolecule #1: Coxsackievirus A6

SupramoleculeName: Coxsackievirus A6 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 86107 / Sci species name: Coxsackievirus A6 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No
Host (natural)Organism: Homo sapiens (human)
Virus shellShell ID: 1 / Name: Coxsackievirus A6 A-particle capsid / T number (triangulation number): 1

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Macromolecule #1: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A6 / Organ: Homo sapiens, human / Tissue: muscle
Molecular weightTheoretical: 33.467273 KDa
SequenceString: NDPIANAVES AVSALADTTI SRVTAANTTA STHSLGTGRV PALQAAETGA SSNASDENLV ETRCVMNRNG VNEASVEHFY SRAGLVGVV EVKDSGTSLD GYTVWPIDVM GFVQQRRKLE LSTYMRFDAE FTFVSNLSNS TTPGMLLQYM YVPPGAPKPD G RKSYQWQT ...String:
NDPIANAVES AVSALADTTI SRVTAANTTA STHSLGTGRV PALQAAETGA SSNASDENLV ETRCVMNRNG VNEASVEHFY SRAGLVGVV EVKDSGTSLD GYTVWPIDVM GFVQQRRKLE LSTYMRFDAE FTFVSNLSNS TTPGMLLQYM YVPPGAPKPD G RKSYQWQT ATNPSVFAKL SDPPPQVSVP FMSPATAYQW FYDGYPTFGE HKQATNLQYG QCPNNMMGHF AIRTVSESTT GK NVHVRVY MRIKHVRAWV PRPLRSQAYM VKNYPTYSQT ITNTATDRAS ITTTDYEGGV PASPQRTS

UniProtKB: Genome polyprotein

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Macromolecule #2: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A6 / Organ: homo sapiens, human / Tissue: muscle
Molecular weightTheoretical: 28.095559 KDa
SequenceString: SPSVEACGYS DRVAQLTVGN STITTQEAAN IVLSYGEWPE YCPSTDATAV DKPTRPDVSV NRFYTLSTKS WKTESTGWYW KFPDVLNDT GVFGQNAQFH YLYRSGFCMH VQCNASKFHQ GALLVAAIPE FVIAASSPAT KPNGRGLYPD FAHTNPGKDG Q EFRDPYVL ...String:
SPSVEACGYS DRVAQLTVGN STITTQEAAN IVLSYGEWPE YCPSTDATAV DKPTRPDVSV NRFYTLSTKS WKTESTGWYW KFPDVLNDT GVFGQNAQFH YLYRSGFCMH VQCNASKFHQ GALLVAAIPE FVIAASSPAT KPNGRGLYPD FAHTNPGKDG Q EFRDPYVL DAGIPLSQAL VFPHQWINLR TNNCATIIMP YVNALPFDSA LNHSNFGLVV IPISPLKYCN GATTEVPVTL TI APLNSEF SGLRQAIKQ

UniProtKB: Genome polyprotein

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Macromolecule #3: Genome polyprotein

MacromoleculeName: Genome polyprotein / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A6 / Organ: homo sapiens, human / Tissue: muscle
Molecular weightTheoretical: 26.274836 KDa
SequenceString: GFPTELKPGT NQFLTTDDGT SPPILPGFEP TPLIHIPGEF TSLLDLCQIE TILEVNNTTG TIGVSRLLIP VRAQNNVDQL CASFQVDPG RNGPWQSTMV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LIAYTPPGSA QPATREAAML GTHIVWDFGL Q SSVTLVIP ...String:
GFPTELKPGT NQFLTTDDGT SPPILPGFEP TPLIHIPGEF TSLLDLCQIE TILEVNNTTG TIGVSRLLIP VRAQNNVDQL CASFQVDPG RNGPWQSTMV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LIAYTPPGSA QPATREAAML GTHIVWDFGL Q SSVTLVIP WISNTHFRAV KIGGVYDYYA TGIVTIWYQT NFVVPPDTPT EANIIALGAA QKNFTLKLCK DTDEIQQTAA YQ

UniProtKB: Genome polyprotein

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1.4 mg/mL
BufferpH: 7.4 / Component - Concentration: 20.0 mmol/L / Component - Name: PBS
Details: NaCl 137mmol/L, KCl 2.7mmol/L, Na2HPO4 10mmol/L, KH2PO4 2mmol/L
GridModel: Quantifoil R2/2 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV
Details: 3?L of virus sample was applied and blot for 6 seconds before plunging..

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Electron microscopy

MicroscopeFEI TECNAI F30
Image recordingFilm or detector model: FEI FALCON II (4k x 4k) / Detector mode: INTEGRATING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Digitization - Frames/image: 1-7 / Number grids imaged: 3 / Number real images: 203 / Average exposure time: 1.0 sec. / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Calibrated defocus max: 4.3 µm / Calibrated defocus min: 1.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.3 mm / Nominal defocus max: 4.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 93000
Sample stageSpecimen holder model: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER
Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 13545
Startup modelType of model: OTHER / Details: Startup model was generated by sotfware AUTO3DEM
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 1.4) / Number images used: 7152
Initial angle assignmentType: COMMON LINE / Software - Name: RELION (ver. 1.4)
Final angle assignmentType: COMMON LINE / Software - Name: RELION (ver. 1.4)
Final 3D classificationNumber classes: 4 / Software - Name: RELION (ver. 1.4)
FSC plot (resolution estimation)

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Atomic model buiding 1

RefinementSpace: REAL / Protocol: AB INITIO MODEL / Overall B value: 163.92 / Target criteria: Correlation coefficient
Output model

PDB-5xs4:
Structure of Coxsackievirus A6 (CVA6) virus A-particle

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