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- EMDB-9604: The structure of CVA10 mature virion in complex with Fab 2G8 -

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Basic information

Entry
Database: EMDB / ID: EMD-9604
TitleThe structure of CVA10 mature virion in complex with Fab 2G8
Map dataNone
SampleCVA10 mature virion in complex with Fab 2G8 != Coxsackievirus A10

CVA10 mature virion in complex with Fab 2G8

  • Virus: Coxsackievirus A10
    • Protein or peptide: VL of Fab 2G8
    • Protein or peptide: VH of Fab 2G8
    • Protein or peptide: VP1
    • Protein or peptide: VP2
    • Protein or peptide: VP3
    • Protein or peptide: VP4
  • Ligand: SPHINGOSINE
KeywordsCVA10 / 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 / nucleoside-triphosphate phosphatase / channel activity / viral capsid / monoatomic ion transmembrane transport / host cell cytoplasm / 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 / cytoplasm
Similarity search - Function
Picornavirus coat protein VP4 superfamily / 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 superfamily / 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
Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesMus musculus (house mouse) / Coxsackievirus A10
Methodsingle particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsZhu R / Zheng QB
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 General Medical Sciences (NIH/NIGMS)1U24GM116792 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 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 28, 2018-
Header (metadata) releaseNov 21, 2018-
Map releaseNov 21, 2018-
UpdateMay 29, 2024-
Current statusMay 29, 2024Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0362
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.0362
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6ad0
  • Surface level: 0.0362
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6ad0
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_9604.png

Downloads & links

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Map

FileDownload / File: emd_9604.map.gz / Format: CCP4 / Size: 824 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 600 pix.
= 676.8 Å		1.13 Å/pix.
x 600 pix.
= 676.8 Å		1.13 Å/pix.
x 600 pix.
= 676.8 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

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0362 / Movie #1: 0.0362
Minimum - Maximum-0.10955997 - 0.20438156
Average (Standard dev.)0.0005581341 (±0.009421075)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions600600600
Spacing600600600
CellA=B=C: 676.8 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.1281.1281.128
M x/y/z600600600
origin x/y/z0.0000.0000.000
length x/y/z676.800676.800676.800
α/β/γ90.00090.00090.000
start NX/NY/NZ-6-10-25
NX/NY/NZ564636
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS600600600
D min/max/mean-0.1100.2040.001

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Supplemental data

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Sample components

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Entire : CVA10 mature virion in complex with Fab 2G8

EntireName: CVA10 mature virion in complex with Fab 2G8
Components
  • Virus: Coxsackievirus A10
    • Protein or peptide: VL of Fab 2G8
    • Protein or peptide: VH of Fab 2G8
    • 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-#6 / 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: VL of Fab 2G8

MacromoleculeName: VL of Fab 2G8 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 12.391881 KDa
SequenceString:
DVLMTQTPLS LPVSLGHQAS ISCRSSQSIV HSNGNTYLEW YLQKPGQSPK LLIYTVSNRF SGVPDRFSGS GSGTDFTLRI TSVEAEDLG VYYCFQGSHI PYTFGGGTKL EIKR

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Macromolecule #2: VH of Fab 2G8

MacromoleculeName: VH of Fab 2G8 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 13.149508 KDa
SequenceString:
EVQLQQSGPD LVKTGASVRV SCRASGYSFT SYYIHWVRLN HGKSLEWIGY INCYNGDITY NQKFKGKASF TLDTSSSTAY MEFNRLTSE DSAVYYCTRE RYGTPHYHFD VWGAGP

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Macromolecule #3: VP1

MacromoleculeName: VP1 / type: protein_or_peptide / ID: 3 / 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

UniProtKB: Genome polyprotein

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Macromolecule #4: VP2

MacromoleculeName: VP2 / type: protein_or_peptide / ID: 4 / 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

UniProtKB: Genome polyprotein

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Macromolecule #5: VP3

MacromoleculeName: VP3 / type: protein_or_peptide / ID: 5 / 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

UniProtKB: Genome polyprotein

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Macromolecule #6: VP4

MacromoleculeName: VP4 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Coxsackievirus A10
Molecular weightTheoretical: 7.464104 KDa
SequenceString:
MGAQVSTQKS GSHETGNVAT GGSTINFTNI NYYKDSYAAS ATRQDFTQDP KKFTQPVLDS IRELSAPLN

UniProtKB: Genome polyprotein

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Macromolecule #7: SPHINGOSINE

MacromoleculeName: SPHINGOSINE / type: ligand / ID: 7 / Number of copies: 1 / Formula: SPH
Molecular weightTheoretical: 299.492 Da
Chemical component information

ChemComp-SPH:
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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TECNAI F30
Image recordingFilm or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 36555
Initial angle assignmentType: OTHER
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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