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- EMDB-11061: Structure of EV71 in complex with a protective antibody 38-3-11A Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-11061
TitleStructure of EV71 in complex with a protective antibody 38-3-11A Fab
Map data
Sample
  • Virus: Enterovirus A71 in complex with a protective antibody 38-3-11A Fab
    • Complex: Enterovirus A71Enterovirus 71
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
      • Protein or peptide: VP4
    • Complex: protective antibody 38-3-11A Fab
      • Protein or peptide: heavy chain
      • Protein or peptide: light chain
  • 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 / Genome polyprotein / Polyprotein
Similarity search - Component
Biological speciesEnterovirus A71 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsZhou D / Fry EE / Ren J / Stuart DI
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 28, 2020-
Current statusOct 28, 2020Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.08
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  • Surface view colored by radius
  • Surface level: 0.08
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  • Surface view with fitted model
  • Atomic models: PDB-6z3p
  • Surface level: 0.08
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6z3p
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_11061.png

Downloads & links

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Map

FileDownload / File: emd_11061.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 1.05 Å
Density
Contour LevelBy AUTHOR: 0.08 / Movie #1: 0.08
Minimum - Maximum-0.22727624 - 0.4214755
Average (Standard dev.)0.0021956097 (±0.028691584)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 461.99997 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.051.051.05
M x/y/z440440440
origin x/y/z0.0000.0000.000
length x/y/z462.000462.000462.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS440440440
D min/max/mean-0.2270.4210.002

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Supplemental data

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Sample components

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Entire : Enterovirus A71 in complex with a protective antibody 38-3-11A Fab

EntireName: Enterovirus A71 in complex with a protective antibody 38-3-11A FabEnterovirus 71
Components
  • Virus: Enterovirus A71 in complex with a protective antibody 38-3-11A Fab
    • Complex: Enterovirus A71Enterovirus 71
      • Protein or peptide: VP1
      • Protein or peptide: VP2
      • Protein or peptide: VP3
      • Protein or peptide: VP4
    • Complex: protective antibody 38-3-11A Fab
      • Protein or peptide: heavy chain
      • Protein or peptide: light chain
  • Ligand: SPHINGOSINE

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Supramolecule #1: Enterovirus A71 in complex with a protective antibody 38-3-11A Fab

SupramoleculeName: Enterovirus A71 in complex with a protective antibody 38-3-11A Fab
type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No

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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: protective antibody 38-3-11A Fab

SupramoleculeName: protective antibody 38-3-11A Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #5-#6
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: 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

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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

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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

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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

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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: 26.175559 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSE VQLVQSGAEV KKPGESLKIS CKGSGYSFTS YWIGWVRQMP GKGLEWMGII YPGDSDTRYS PSFQGQVTI SADKSISTAY LQWSSLKASD TAMYYCARLH SSSWFYGMDV WGQGTTVTVS SASTKGPSVF PLAPSSKSTS G GTAALGCL ...String:
MGWSCIILFL VATATGVHSE VQLVQSGAEV KKPGESLKIS CKGSGYSFTS YWIGWVRQMP GKGLEWMGII YPGDSDTRYS PSFQGQVTI SADKSISTAY LQWSSLKASD TAMYYCARLH SSSWFYGMDV WGQGTTVTVS SASTKGPSVF PLAPSSKSTS G GTAALGCL VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EP KSCDK

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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: 25.288203 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGWSCIILFL VATATGVHSD IQMTQSPSSL SASVGDRVTI TCRASQSISS YLNWYQQKPG KAPKLLIYAA SSLQSGVPSR FSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPRTFGP GTKVDIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY P REAKVQWK ...String:
MGWSCIILFL VATATGVHSD IQMTQSPSSL SASVGDRVTI TCRASQSISS YLNWYQQKPG KAPKLLIYAA SSLQSGVPSR FSGSGSGTD FTLTISSLQP EDFATYYCQQ SYSTPRTFGP GTKVDIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY P REAKVQWK VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGEC

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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 / 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-PROPANE

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Electron microscopy

MicroscopeTFS KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 41.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

3vbs

Initial angle assignmentType: RANDOM ASSIGNMENT
Final 3D classificationNumber classes: 4
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 14430

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Atomic model buiding 1

RefinementProtocol: RIGID BODY FIT
Output model

PDB-6z3p:
Structure of EV71 in complex with a protective antibody 38-3-11A Fab

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