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- EMDB-0888: The cryo-EM structure of coxsackievirus A16 A-particle -

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Basic information

Entry
Database: EMDB / ID: EMD-0888
TitleThe cryo-EM structure of coxsackievirus A16 A-particle
Map dataThe cryo-EM structure of coxsackievirus A16 A-particle
Sample
  • Virus: Coxsackievirus A16
    • Protein or peptide: VP1
    • Protein or peptide: VP2
    • Protein or peptide: VP3
KeywordsVIRUS
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 / symbiont-mediated suppression of host NF-kappaB cascade / monoatomic ion transmembrane transport / DNA replication / 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 / membrane / metal ion binding
Similarity search - Function
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) ...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 / Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesCoxsackievirus A16
Methodsingle particle reconstruction / cryo EM / Resolution: 3.33 Å
AuthorsHe MZ / Xu LF
Funding support China, United States, 9 items
OrganizationGrant numberCountry
National Natural Science Foundation of China81991490 China
National Science Foundation (China)2018ZX09711003-005-003 China
National Science Foundation (China)2017ZX10304402-002-003 China
National Natural Science Foundation of China31670933 China
National Natural Science Foundation of China81801646 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
CitationJournal: Cell Host Microbe / Year: 2020
Title: Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16.
Authors: Maozhou He / Longfa Xu / Qingbing Zheng / Rui Zhu / Zhichao Yin / Zhenghui Zha / Yu Lin / Lisheng Yang / Yang Huang / Xiangzhong Ye / Shuxuan Li / Wangheng Hou / Yangtao Wu / Jinle Han / ...Authors: Maozhou He / Longfa Xu / Qingbing Zheng / Rui Zhu / Zhichao Yin / Zhenghui Zha / Yu Lin / Lisheng Yang / Yang Huang / Xiangzhong Ye / Shuxuan Li / Wangheng Hou / Yangtao Wu / Jinle Han / Dongxiao Liu / Zekai Li / Zhenqin Chen / Hai Yu / Yuqiong Que / Yingbin Wang / Xiaodong Yan / Jun Zhang / Ying Gu / Z Hong Zhou / Tong Cheng / Shaowei Li / Ningshao Xia /
Abstract: Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific ...Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens.
History
DepositionDec 7, 2019-
Header (metadata) releaseFeb 5, 2020-
Map releaseFeb 5, 2020-
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: 0.6435
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.6435
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6lhb
  • Surface level: 0.6435
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6lhb
  • 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_0888.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThe cryo-EM structure of coxsackievirus A16 A-particle
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.13 Å/pix.
x 400 pix.
= 451.2 Å
1.13 Å/pix.
x 400 pix.
= 451.2 Å
1.13 Å/pix.
x 400 pix.
= 451.2 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: 0.6435 / Movie #1: 0.6435
Minimum - Maximum-1.162255 - 2.7617776
Average (Standard dev.)0.036574554 (±0.21135618)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 451.2 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.1281.1281.128
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z451.200451.200451.200
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-1.1622.7620.037

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Supplemental data

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Sample components

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Entire : Coxsackievirus A16

EntireName: Coxsackievirus A16
Components
  • Virus: Coxsackievirus A16
    • Protein or peptide: VP1
    • Protein or peptide: VP2
    • Protein or peptide: VP3

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Supramolecule #1: Coxsackievirus A16

SupramoleculeName: Coxsackievirus A16 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 31704 / Sci species name: Coxsackievirus A16 / 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 A16
Molecular weightTheoretical: 33.106352 KDa
SequenceString: GDPIADMIDQ TVNNQVNRSL TALQVLPTAA NTEASSHRLG TGVVPALQAA ETGASSNASD KNLIETRCVL NHHSTQETAI GNFFSRAGL VSIITMPTTD TQNTDGYVNW DIDLMGYAQL RRKCELFTYM RFDAEFTFVV AKPNGVLVPQ LLQYMYVPPG A PKPTSRDS ...String:
GDPIADMIDQ TVNNQVNRSL TALQVLPTAA NTEASSHRLG TGVVPALQAA ETGASSNASD KNLIETRCVL NHHSTQETAI GNFFSRAGL VSIITMPTTD TQNTDGYVNW DIDLMGYAQL RRKCELFTYM RFDAEFTFVV AKPNGVLVPQ LLQYMYVPPG A PKPTSRDS FAWQTATNPS VFVKMTDPPA QVSVPFMSPA SAYQWFYDGY PTFGEHLQAN DLDYGQCPNN MMGTFSIRTV GT EKSPHSI TLRVYMRIKH VRAWIPRPLR NQPYLFKTNP NYKGNDIKCT STSRDKITTL

UniProtKB: Genome polyprotein

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Macromolecule #2: VP2

MacromoleculeName: VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Coxsackievirus A16
Molecular weightTheoretical: 27.557104 KDa
SequenceString: SPSAEACGYS DRVAQLTIGN STITTQEAAN IVIAYGEWPE YCPDTDATAV DKPTRPDVSV NRFFTLDTKS WAKDSKGWYW KFPDVLTEV GVFGQNAQFH YLYRSGFCVH VQCNASKFHQ GALLVAVLPE YVLGTIAGGT GNENSHPPYA TTQPGQVGAV L THPYVLDA ...String:
SPSAEACGYS DRVAQLTIGN STITTQEAAN IVIAYGEWPE YCPDTDATAV DKPTRPDVSV NRFFTLDTKS WAKDSKGWYW KFPDVLTEV GVFGQNAQFH YLYRSGFCVH VQCNASKFHQ GALLVAVLPE YVLGTIAGGT GNENSHPPYA TTQPGQVGAV L THPYVLDA GIPLSQLTVC PHQWINLRTN NCATIIVPYM NTVPFDSALN HCNFGLLVIP VVPLDFNAGA TSEIPITVTI AP MCAEFAG LRQAVKQ

UniProtKB: Genome polyprotein

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Macromolecule #3: VP3

MacromoleculeName: VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Coxsackievirus A16
Molecular weightTheoretical: 26.654295 KDa
SequenceString: GIPTELKPGT NQFLTTDDGV SAPILPGFHP TPPIHIPGEV HNLLEICRVE TILEVNNLKT NETTPMQRLC FPVSVQSKTG ELCAAFRAD PGRDGPWQST ILGQLCRYYT QWSGSLEVTF MFAGSFMATG KMLIAYTPPG GNVPADRITA MLGTHVIWDF G LQSSVTLV ...String:
GIPTELKPGT NQFLTTDDGV SAPILPGFHP TPPIHIPGEV HNLLEICRVE TILEVNNLKT NETTPMQRLC FPVSVQSKTG ELCAAFRAD PGRDGPWQST ILGQLCRYYT QWSGSLEVTF MFAGSFMATG KMLIAYTPPG GNVPADRITA MLGTHVIWDF G LQSSVTLV VPWISNTHYR AHARAGYFDY YTTGIITIWY QTNYVVPIGA PTTAYIVALA AAQDNFTMKL CKDTEDIEQT AN IQ

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

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) / Detector mode: INTEGRATING / Average electron dose: 40.0 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: 3.33 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 3409
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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