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- EMDB-11062: Structure of EV71 in complex with a protective antibody 38-1-10A Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-11062
TitleStructure of EV71 in complex with a protective antibody 38-1-10A Fab
Map dataOccupancy of Fab is lower, use contour level 0.03 to view
Sample
  • Virus: Enterovirus A71 with Human antibody
    • Complex: Enterovirus A71
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
      • Protein or peptide: VP4
    • Complex: Human antibody
      • Protein or peptide: Heavy chain
      • Protein or peptide: Light chain
  • Ligand: SPHINGOSINE
KeywordsEV71 / antibody 38-3-11A / antibody 38-1-10A / EV71-Fab complex / 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 / 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 / Genome polyprotein / Polyprotein
Similarity search - Component
Biological speciesEnterovirus A71 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.7 Å
AuthorsZhou D / Fry EE
Funding support United Kingdom, 2 items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MR/N00065X/1 United Kingdom
Wellcome Trust101122/Z/13/Z United Kingdom
CitationJournal: Nat Commun / Year: 2020
Title: Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71.
Authors: Kuan-Ying A Huang / Daming Zhou / Elizabeth E Fry / Abhay Kotecha / Peng-Nien Huang / Shu-Li Yang / Kuo-Chien Tsao / Yhu-Chering Huang / Tzou-Yien Lin / Jingshan Ren / David I Stuart /
Abstract: Enterovirus 71 (EV71)-neutralizing antibodies correlate with protection and have potential as therapeutic agents. We isolate and characterize a panel of plasmablast-derived monoclonal antibodies from ...Enterovirus 71 (EV71)-neutralizing antibodies correlate with protection and have potential as therapeutic agents. We isolate and characterize a panel of plasmablast-derived monoclonal antibodies from an infected child whose antibody response focuses on the plateau epitope near the icosahedral 3-fold axes. Eight of a total of 19 antibodies target this epitope and three of these potently neutralize the virus. Representative neutralizing antibodies 38-1-10A and 38-3-11A both confer effective protection against lethal EV71 challenge in hSCARB2-transgenic mice. The cryo-electron microscopy structures of the EV71 virion in complex with Fab fragments of these potent and protective antibodies reveal the details of a conserved epitope formed by residues in the BC and HI loops of VP2 and the BC and HI loops of VP3 spanning the region around the 3-fold axis. Remarkably, the two antibodies interact with the epitope in quite distinct ways. These plateau-binding antibodies provide templates for promising candidate therapeutics.
History
DepositionMay 21, 2020-
Header (metadata) releaseSep 2, 2020-
Map releaseSep 2, 2020-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.06
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.06
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6z3q
  • Surface level: 0.05
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6z3q
  • 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_11062.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationOccupancy of Fab is lower, use contour level 0.03 to view
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.35 Å/pix.
x 400 pix.
= 540. Å
1.35 Å/pix.
x 400 pix.
= 540. Å
1.35 Å/pix.
x 400 pix.
= 540. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.35 Å
Density
Contour LevelBy AUTHOR: 0.06 / Movie #1: 0.06
Minimum - Maximum-0.18079954 - 0.3029493
Average (Standard dev.)0.0012159126 (±0.01825437)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 540.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.351.351.35
M x/y/z400400400
origin x/y/z0.0000.0000.000
length x/y/z540.000540.000540.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS400400400
D min/max/mean-0.1810.3030.001

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Supplemental data

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Sample components

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Entire : Enterovirus A71 with Human antibody

EntireName: Enterovirus A71 with Human antibody
Components
  • Virus: Enterovirus A71 with Human antibody
    • Complex: Enterovirus A71
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
      • Protein or peptide: VP4
    • Complex: Human antibody
      • Protein or peptide: Heavy chain
      • Protein or peptide: Light chain
  • Ligand: SPHINGOSINE

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Supramolecule #1: Enterovirus A71 with Human antibody

SupramoleculeName: Enterovirus A71 with Human antibody / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No
Host (natural)Organism: Homo sapiens (human)

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Supramolecule #2: Enterovirus A71

SupramoleculeName: Enterovirus A71 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#4
Source (natural)Organism: Enterovirus A71

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Supramolecule #3: Human antibody

SupramoleculeName: Human antibody / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #5-#6
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: VP1

MacromoleculeName: VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: picornain 2A
Source (natural)Organism: Enterovirus A71
Molecular weightTheoretical: 32.781805 KDa
SequenceString: GDRVADMIES SIGNSVSRAL TQALPAPTGQ NTQVSSHRLD TGEVPALQAA EIGASSNTSD ESMIETRCVL NSHSTAETTL DSFFSRAGL VGEIDLPLEG TTNPNGYANW DIDITGYAQM RRKVELFTYM RFDAEFTFVA CTPTGQVVPQ LLQYMFVPPG A PKPESRES ...String:
GDRVADMIES SIGNSVSRAL TQALPAPTGQ NTQVSSHRLD TGEVPALQAA EIGASSNTSD ESMIETRCVL NSHSTAETTL DSFFSRAGL VGEIDLPLEG TTNPNGYANW DIDITGYAQM RRKVELFTYM RFDAEFTFVA CTPTGQVVPQ LLQYMFVPPG A PKPESRES LAWQTATNPS VFVKLTDPPA QVSVPFMSPA SAYQWFYDGY PTFGEHKQEK DLEYGACPNN MMGTFSVRTV GS SKSKYAL VVRIYMRMKH VRAWIPRPMR NQNYLFKANP NYAGDSIKPT GTSRNAITTL

UniProtKB: Genome polyprotein

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Macromolecule #2: VP2

MacromoleculeName: VP2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Enterovirus A71
Molecular weightTheoretical: 27.784213 KDa
SequenceString: SPSAEACGYS DRVAQLTIGN STITTQEAAN IIVGYGEWPS YCSDDDATAV DKPTRPDVSV NRFYTLDTKL WEKSSKGWYW KFPDVLTET GVFGQNAQFH YLYRSGFCIH VQCNASKFHQ GALLVAILPE YVIGTVAGGT GTEDSHPPYI QTQPGADGFE L QHPYVLDA ...String:
SPSAEACGYS DRVAQLTIGN STITTQEAAN IIVGYGEWPS YCSDDDATAV DKPTRPDVSV NRFYTLDTKL WEKSSKGWYW KFPDVLTET GVFGQNAQFH YLYRSGFCIH VQCNASKFHQ GALLVAILPE YVIGTVAGGT GTEDSHPPYI QTQPGADGFE L QHPYVLDA GIPISQLTVC PHQWINLRTN NCATIIVPYM NTLPFDSALN HCNFGLLVVP ISPLDFDQGA TPVIPITITL AP MCSEFAG LRQAVTQ

UniProtKB: Genome polyprotein

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Macromolecule #3: VP3

MacromoleculeName: VP3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Enterovirus A71
Molecular weightTheoretical: 26.540332 KDa
SequenceString: GFPTELKPGT NQFLTTDDGV SAPILPNFHP TPCIHIPGEV RNLLELCQVE TILEVNNVPT NATSLMERLR FPVSAQAGKG ELCAVFRAD PGRDGPWQST MLGQLCGYYT QWSGSLEVTF MFTGSFMATG KMLIAYTPPG GPLPKDRATA MLGTHVIWDF G LQSSVTLV ...String:
GFPTELKPGT NQFLTTDDGV SAPILPNFHP TPCIHIPGEV RNLLELCQVE TILEVNNVPT NATSLMERLR FPVSAQAGKG ELCAVFRAD PGRDGPWQST MLGQLCGYYT QWSGSLEVTF MFTGSFMATG KMLIAYTPPG GPLPKDRATA MLGTHVIWDF G LQSSVTLV IPWISNTHYR AHARDGVFDY YTTGLVSIWY QTNYVVPIGA PNTAYIIALA AAQKNFTMKL CKDTSHILQT AS IQ

UniProtKB: Genome polyprotein

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Macromolecule #4: VP4

MacromoleculeName: VP4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Enterovirus A71
Molecular weightTheoretical: 6.380943 KDa
SequenceString:
SHENSNSATE GSTINYTTIN YYKDSYAATA GKQSLKQDPD KFANPVKDIF TEMAAPLK

UniProtKB: Polyprotein

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Macromolecule #5: Heavy chain

MacromoleculeName: Heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 25.216357 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGCVAQLQLQ ESGPGLVKPS ETLSLTCTVS GGSISSSSYY WGWIRQPPGK GLEWIGSIYY SGSTYYNPSL KSRVTISVDT SKNQFSLKL SSVTAADTAV YYCAREITMI AWFDPWGQGT LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String:
MGCVAQLQLQ ESGPGLVKPS ETLSLTCTVS GGSISSSSYY WGWIRQPPGK GLEWIGSIYY SGSTYYNPSL KSRVTISVDT SKNQFSLKL SSVTAADTAV YYCAREITMI AWFDPWGQGT LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSS(UNK)LY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC DKHHHHHH

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Macromolecule #6: Light chain

MacromoleculeName: Light chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.77049 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGCVADIQMT QSPSSLSASV GDRVTITCRA SQGIRNDLGW YQQKPGKAPK LLIYAASSLQ SGVPSRFSGS GSGTDFTLTI SSLQPEDFA TYYCLQDYNY LLTFGGGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String:
MGCVADIQMT QSPSSLSASV GDRVTITCRA SQGIRNDLGW YQQKPGKAPK LLIYAASSLQ SGVPSRFSGS GSGTDFTLTI SSLQPEDFA TYYCLQDYNY LLTFGGGTKV EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C

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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 POLARA 300
Image recordingFilm or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 30.0 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 Polara / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 10074
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: ANGULAR RECONSTITUTION
Final 3D classificationNumber classes: 4

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