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- EMDB-9600: The structure of CVA10 virus mature virion -

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Basic information

Entry
Database: EMDB / ID: EMD-9600
TitleThe structure of CVA10 virus mature virion
Map dataNone
Sample
  • Virus: Coxsackievirus A10
    • Protein or peptide: VP1
    • Protein or peptide: VP2
    • Protein or peptide: VP3
    • Protein or peptide: VP4
  • Ligand: SPHINGOSINE
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 / endocytosis involved in viral entry into host cell / cytoplasmic vesicle membrane / : ...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 / endocytosis involved in viral entry into host cell / cytoplasmic vesicle membrane / : / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / symbiont-mediated suppression of host gene expression / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / DNA-templated transcription / host cell nucleus / structural molecule activity / virion attachment to host cell / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding
Similarity search - Function
Picornavirus coat protein VP4 superfamily / 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) ...Picornavirus coat protein VP4 superfamily / 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) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / 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 / DNA/RNA polymerase superfamily / Peptidase S1, PA clan / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesCoxsackievirus A10
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsCui YX / Zheng QB / Zhu R / Xu LF / Li SW / Yan XD / Zhou ZH / Cheng T
Funding support China, United States, 9 items
OrganizationGrant numberCountry
National Natural Science Foundation of China31670933 China
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R37-GM33050 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM071940 United States
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)DE025567 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI094386 United States
National Institutes of Health/National Center for Research Resources (NIH/NCRR)1S10RR23057 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1U24GM116792 United States
National Science Foundation (United States)DBI-1338135 United States
National Science Foundation (United States)DMR-1548924 United States
CitationJournal: 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
DepositionJul 27, 2018-
Header (metadata) releaseNov 21, 2018-
Map releaseNov 21, 2018-
UpdateMar 23, 2022-
Current statusMar 23, 2022Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0758
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.0758
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6acu
  • Surface level: 0.0758
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6acu
  • 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_9600.map.gz / Format: CCP4 / Size: 244.1 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.)
1.34 Å/pix.
x 400 pix.
= 536. Å
1.34 Å/pix.
x 400 pix.
= 536. Å
1.34 Å/pix.
x 400 pix.
= 536. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.34 Å
Density
Contour LevelBy AUTHOR: 0.0758 / Movie #1: 0.0758
Minimum - Maximum-0.1836173 - 0.2990314
Average (Standard dev.)0.0008821706 (±0.018083135)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin333
Dimensions400400400
Spacing400400400
CellA=B=C: 536.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.341.341.34
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z536.000536.000536.000
α/β/γ90.00090.00090.000
start NX/NY/NZ-38-19-20
NX/NY/NZ858082
MAP C/R/S123
start NC/NR/NS333
NC/NR/NS400400400
D min/max/mean-0.1840.2990.001

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Supplemental data

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Sample components

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Entire : Coxsackievirus A10

EntireName: Coxsackievirus A10
Components
  • Virus: Coxsackievirus A10
    • Protein or peptide: VP1
    • Protein or peptide: VP2
    • Protein or peptide: VP3
    • Protein or peptide: VP4
  • Ligand: SPHINGOSINE

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Supramolecule #1: Coxsackievirus A10

SupramoleculeName: Coxsackievirus A10 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 / NCBI-ID: 42769 / Sci species name: Coxsackievirus A10 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No

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Macromolecule #1: VP1

MacromoleculeName: VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A10
Molecular weightTheoretical: 33.15923 KDa
SequenceString: GDPVEDIIHD ALGNTARRAI SSATNVESAA NTTPSSHRLE TGRVPALQAA ETGATSNATD ENMIETRCVV NRNGVLETTI NHFFSRSGL VGVVNLTDGG TDTTGYATWD IDIMGFVQLR RKCEMFTYMR FNAEFTFVTT TENGGARPYM LQYMYVPPGA P KPTGRDAF ...String:
GDPVEDIIHD ALGNTARRAI SSATNVESAA NTTPSSHRLE TGRVPALQAA ETGATSNATD ENMIETRCVV NRNGVLETTI NHFFSRSGL VGVVNLTDGG TDTTGYATWD IDIMGFVQLR RKCEMFTYMR FNAEFTFVTT TENGGARPYM LQYMYVPPGA P KPTGRDAF QWQTATNPSV FVKLTDPPAQ VSVPFMSPAS AYQWFYDGYP TFGQHPETSN TTYGLCPNNM MGTFAVRVVS RE ASQLKLQ TRVYMKLKHV RAWVPRPIRS QPYLLKNFPN YDSSKITNSA RDRSSIKQAN M

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Macromolecule #2: VP2

MacromoleculeName: VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A10
Molecular weightTheoretical: 27.808133 KDa
SequenceString: SPSVEACGYS DRVAQLTVGN SSITTQEAAN IVLAYGEWPE YCPDTDATAV DKPTRPDVSV NRFYTLDSKM WQENSTGWYW KFPDVLNKT GVFGQNAQFH YLYRSGFCLH VQCNASKFHQ GALLVAVIPE FVIAGRGSNT KPNEAPHPGF TTTFPGTTGA T FYDPYVLD ...String:
SPSVEACGYS DRVAQLTVGN SSITTQEAAN IVLAYGEWPE YCPDTDATAV DKPTRPDVSV NRFYTLDSKM WQENSTGWYW KFPDVLNKT GVFGQNAQFH YLYRSGFCLH VQCNASKFHQ GALLVAVIPE FVIAGRGSNT KPNEAPHPGF TTTFPGTTGA T FYDPYVLD SGVPLSQALI YPHQWINLRT NNCATVIVPY INAVPFDSAI NHSNFGLIVI PVSPLKYSSG ATTAIPITIT IA PLNSEFG GLRQAVSQ

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Macromolecule #3: VP3

MacromoleculeName: VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A10
Molecular weightTheoretical: 26.129588 KDa
SequenceString: GIPAELRPGT NQFLTTDDGT AAPILPGFTP TPTIHIPGEV HSLLELCRVE TILEVNNTTE ATGLTRLLIP VSSQNKADEL CAAFMVDPG RIGPWQSTLV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LVAYSPPGSA QPANRETAML GTHVIWDFGL Q SSVSLVIP ...String:
GIPAELRPGT NQFLTTDDGT AAPILPGFTP TPTIHIPGEV HSLLELCRVE TILEVNNTTE ATGLTRLLIP VSSQNKADEL CAAFMVDPG RIGPWQSTLV GQICRYYTQW SGSLKVTFMF TGSFMATGKM LVAYSPPGSA QPANRETAML GTHVIWDFGL Q SSVSLVIP WISNTHFRTA KTGGNYDYYT AGVVTLWYQT NYVVPPETPG EAYIIAMGAA QDNFTLKICK DTDEVTQQAV LQ

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Macromolecule #4: VP4

MacromoleculeName: VP4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A10
Molecular weightTheoretical: 7.464104 KDa
SequenceString:
MGAQVSTQKS GSHETGNVAT GGSTINFTNI NYYKDSYAAS ATRQDFTQDP KKFTQPVLDS IRELSAPLN

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Macromolecule #5: SPHINGOSINE

MacromoleculeName: SPHINGOSINE / type: ligand / ID: 5 / Number of copies: 1 / Formula: SPH
Molecular weightTheoretical: 299.492 Da
Chemical component information

ChemComp-SPH:
SPHINGOSINE / Sphingosine

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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

Concentration2.0 mg/mL
BufferpH: 7.4
GridModel: Quantifoil R2/2 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K2 (4k x 4k) / Average electron dose: 60.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: Gctf
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 17092
FSC plot (resolution estimation)

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