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- EMDB-0894: The cryo-EM structure of coxsackievirus A16 mature virion in comp... -

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Basic information

Entry
Database: EMDB / ID: EMD-0894
TitleThe cryo-EM structure of coxsackievirus A16 mature virion in complex with Fab 14B10
Map dataThe cryo-EM structure of coxsackievirus A16 mature virion in complex with Fab 14B10
Sample
  • Complex: Coxsackievirus A16 complex
    • Complex: Fab antibody
      • Protein or peptide: light chain variable region of Fab 14B10
      • Protein or peptide: heavy chain variable region of Fab 14B10
    • Complex: Coxsackievirus A16
      • Protein or peptide: VP1 protein
      • Protein or peptide: VP2 protein
      • Protein or peptide: VP3 protein
      • Protein or peptide: VP4 protein
  • 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 / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / viral capsid ...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 / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / symbiont-mediated suppression of host gene expression / DNA replication / 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 / membrane / metal ion binding / cytoplasm
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 / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Genome polyprotein / Genome polyprotein / Genome polyprotein / VP4 protein / Genome polyprotein
Similarity search - Component
Biological speciesMus musculus (house mouse) / Coxsackievirus A16
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsHe MZ / Xu LF / Zheng QB / Zhu R / Yin ZC / Cheng T / Li SW
Funding support China, United States, 9 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81991490 China
National Science Foundation (NSF, China)2017ZX10304402-002-003 China
National Science Foundation (NSF, China)2018ZX09711003-005-003 China
National Natural Science Foundation of China (NSFC)81801646 China
National Natural Science Foundation of China (NSFC)31670933 China
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)R37-GM33050 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI094386 United States
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)DE025567 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 9, 2019-
Header (metadata) releaseFeb 5, 2020-
Map releaseFeb 5, 2020-
UpdateFeb 26, 2020-
Current statusFeb 26, 2020Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.9596
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.9596
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6lhp
  • Surface level: 0.9596
  • Imaged by UCSF Chimera
  • Download
  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6lhp
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_0894.png

Downloads & links

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Map

FileDownload / File: emd_0894.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationThe cryo-EM structure of coxsackievirus A16 mature virion in complex with Fab 14B10
Voxel sizeX=Y=Z: 1.128 Å
Density
Contour LevelBy AUTHOR: 0.9596 / Movie #1: 0.9596
Minimum - Maximum-1.9571326 - 3.8434618
Average (Standard dev.)0.0015189884 (±0.20034708)
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
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS600600600
D min/max/mean-1.9573.8430.002

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Supplemental data

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Sample components

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Entire : Coxsackievirus A16 complex

EntireName: Coxsackievirus A16 complex
Components
  • Complex: Coxsackievirus A16 complex
    • Complex: Fab antibody
      • Protein or peptide: light chain variable region of Fab 14B10
      • Protein or peptide: heavy chain variable region of Fab 14B10
    • Complex: Coxsackievirus A16
      • Protein or peptide: VP1 protein
      • Protein or peptide: VP2 protein
      • Protein or peptide: VP3 protein
      • Protein or peptide: VP4 protein
  • Ligand: SPHINGOSINE

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Supramolecule #1: Coxsackievirus A16 complex

SupramoleculeName: Coxsackievirus A16 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6

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Supramolecule #2: Fab antibody

SupramoleculeName: Fab antibody / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Source (natural)Organism: Mus musculus (house mouse)

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Supramolecule #3: Coxsackievirus A16

SupramoleculeName: Coxsackievirus A16 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#6
Source (natural)Organism: Coxsackievirus A16

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Macromolecule #1: light chain variable region of Fab 14B10

MacromoleculeName: light chain variable region of Fab 14B10 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 11.671961 KDa
SequenceString:
DIQMTQSSSY LSVSLGGRVT ITCKASDHIN NWLAWYQQKP GNAPRLLISG ATSLETGIPS RFSGSGSGKD YTLSITSLQT EDVGTYYCQ QYWSTPTFGG GTKLEIKR

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Macromolecule #2: heavy chain variable region of Fab 14B10

MacromoleculeName: heavy chain variable region of Fab 14B10 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 12.7713 KDa
SequenceString:
QVQLQQSGPE LVKPGASVKI SCKASGYEFS RSWMNWVKQR PGQGLEWIGR IYPGDGDTNY NGKFRDKATL TADKSSSTAY MQLSRLTSV DSAVYFCARR RGYFDVWGAG TTVTVS

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Macromolecule #3: VP1 protein

MacromoleculeName: VP1 protein / type: protein_or_peptide / ID: 3 / Number of copies: 1