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- EMDB-9812: The symmetric-reconstructed cryo-EM structure of Zika virus-FabZK... -

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Basic information

Entry
Database: EMDB / ID: EMD-9812
TitleThe symmetric-reconstructed cryo-EM structure of Zika virus-FabZK2B10 complex
Map data
Sample
  • Complex: ZIKV complexed with FabZK2B10
    • Protein or peptide: ZIKV structural protein E
    • Protein or peptide: strutural protein M
    • Protein or peptide: FabZK2B10 heavy chain
    • Protein or peptide: FabZK2B10 light chain
KeywordsZIKV / antibody / VIRUS
Function / homology
Function and homology information


symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / negative regulation of innate immune response / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / 4 iron, 4 sulfur cluster binding / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / protein dimerization activity / molecular adaptor activity / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / RNA-dependent RNA polymerase activity / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / centrosome / viral envelope / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / structural molecule activity / virion attachment to host cell / GTP binding / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding
Similarity search - Function
: / : / Flavivirus envelope glycoprotein E, stem/anchor domain / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus / Flavivirus non-structural protein NS4A ...: / : / Flavivirus envelope glycoprotein E, stem/anchor domain / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / Envelope glycoprotein M, flavivirus / Flavivirus envelope glycoprotein M / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M superfamily, flavivirus / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / helicase superfamily c-terminal domain / Immunoglobulin E-set / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily / DNA/RNA polymerase superfamily / Peptidase S1, PA clan / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Biological speciesZika virus / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 11.0 Å
AuthorsWang L / Wang RK
CitationJournal: Cell Rep / Year: 2019
Title: Structural Basis for Neutralization and Protection by a Zika Virus-Specific Human Antibody.
Authors: Lin Wang / Ruoke Wang / Lei Wang / Haijing Ben / Lei Yu / Fei Gao / Xuanling Shi / Chibiao Yin / Fuchun Zhang / Ye Xiang / Linqi Zhang /
Abstract: We previously reported a human monoclonal antibody, ZK2B10, capable of protection against Zika virus (ZIKV) infection and microcephaly in developing mouse embryos. Here, we report the structural ...We previously reported a human monoclonal antibody, ZK2B10, capable of protection against Zika virus (ZIKV) infection and microcephaly in developing mouse embryos. Here, we report the structural features and mechanism of action of ZK2B10. The crystal structure at a resolution of 2.32 Å revealed that the epitope is located on the lateral ridge of DIII of the envelope glycoprotein. Cryo-EM structure with mature ZIKV showed that the antibody binds to DIIIs around the icosahedral 2-fold, 3-fold, and 5-fold axes, a distinct feature compared to those reported for DIII-specific antibodies. The binding of ZK2B10 to ZIKV has no detectable effect on viral attachment to target cells or on conformational changes of the E glycoprotein in the acidic environment, suggesting that ZK2B10 functions at steps between the formation of the fusion intermediate and membrane fusion. These results provide structural and mechanistic insights into how ZK2B10 mediates protection against ZIKV infection.
History
DepositionFeb 8, 2019-
Header (metadata) releaseApr 10, 2019-
Map releaseApr 10, 2019-
UpdateMar 27, 2024-
Current statusMar 27, 2024Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 3.45
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 3.45
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6jfi
  • Surface level: 3.45
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6jfi
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_9812.png

Downloads & links

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Map

FileDownload / File: emd_9812.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 2.24 Å
Density
Contour LevelBy AUTHOR: 3.45 / Movie #1: 3.45
Minimum - Maximum-3.081707 - 6.4863596
Average (Standard dev.)0.2303884 (±1.0)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 716.8 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z2.242.242.24
M x/y/z320320320
origin x/y/z0.0000.0000.000
length x/y/z716.800716.800716.800
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS320320320
D min/max/mean-3.0826.4860.230

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Supplemental data

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Sample components

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Entire : ZIKV complexed with FabZK2B10

EntireName: ZIKV complexed with FabZK2B10
Components
  • Complex: ZIKV complexed with FabZK2B10
    • Protein or peptide: ZIKV structural protein E
    • Protein or peptide: strutural protein M
    • Protein or peptide: FabZK2B10 heavy chain
    • Protein or peptide: FabZK2B10 light chain

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Supramolecule #1: ZIKV complexed with FabZK2B10

SupramoleculeName: ZIKV complexed with FabZK2B10 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Zika virus

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Macromolecule #1: ZIKV structural protein E

MacromoleculeName: ZIKV structural protein E / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Zika virus
Molecular weightTheoretical: 54.186762 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: IRCIGVSNRD FVEGMSGGTW VDVVLEHGGC VTVMAQDKPT VDIELVTTTV SNMAEVRSYC YEASISDMAS DSRCPTQGEA YLDKQSDTQ YVCKRTLVDR GWGNGCGLFG KGSLVTCAKF ACSKKMTGKS IQPENLEYRI MLSVHGSQHS GMIVNDTGHE T DENRAKVE ...String:
IRCIGVSNRD FVEGMSGGTW VDVVLEHGGC VTVMAQDKPT VDIELVTTTV SNMAEVRSYC YEASISDMAS DSRCPTQGEA YLDKQSDTQ YVCKRTLVDR GWGNGCGLFG KGSLVTCAKF ACSKKMTGKS IQPENLEYRI MLSVHGSQHS GMIVNDTGHE T DENRAKVE ITPNSPRAEA TLGGFGSLGL DCEPRTGLDF SDLYYLTMNN KHWLVHKEWF HDIPLPWHAG ADTGTPHWNN KE ALVEFKD AHAKRQTVVV LGSQEGAVHT ALAGALEAEM DGAKGRLSSG HLKCRLKMDK LRLKGVSYSL CTAAFTFTKI PAE TLHGTV TVEVQYAGTD GPCKVPAQMA VDMQTLTPVG RLITANPVIT ESTENSKMML ELDPPFGDSY IVIGVGEKKI THHW HRSGS TIGKAFEATV RGAKRMAVLG DTAWDFGSVG GALNSLGKGI HQIFGAAFKS LFGGMSWFSQ ILIGTLLMWL GLNTK NGSI SLMCLALGGV LIFLSTA

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Macromolecule #2: strutural protein M

MacromoleculeName: strutural protein M / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO / EC number: flavivirin
Source (natural)Organism: Zika virus
Molecular weightTheoretical: 8.496883 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS

UniProtKB: Genome polyprotein

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Macromolecule #3: FabZK2B10 heavy chain

MacromoleculeName: FabZK2B10 heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 25.383305 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EVQLVQSGAE VKKPGASVKV SCKASGYTFT SGHTFPSYDI NWVRQATGQG LEWMGWMNPN RGNTGYAQKF QGRVTMTRNT SINTAYMEL SSLRSEDTAV YYCARVRSGT NYGSYYYYYY GMDVWGQGTT VTVSSASTKG PSVFPLAPSS KSTSGGTAAL G CLVKDYFP ...String:
EVQLVQSGAE VKKPGASVKV SCKASGYTFT SGHTFPSYDI NWVRQATGQG LEWMGWMNPN RGNTGYAQKF QGRVTMTRNT SINTAYMEL SSLRSEDTAV YYCARVRSGT NYGSYYYYYY GMDVWGQGTT VTVSSASTKG PSVFPLAPSS KSTSGGTAAL G CLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS SLGTQTYICN VNHKPSNTKV DKRVEPK

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Macromolecule #4: FabZK2B10 light chain

MacromoleculeName: FabZK2B10 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.782035 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SYELTQPPSA SGTPGQRVTI SCSGSSSNIG NNYVHWYQQL PGSAPKLLIY RNNQRPSGVP DRFSGSKSGT SGSLAISGLR SEDEADYYC ASWDDSLSGH WVFGGGTKVT VLGQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT ...String:
SYELTQPPSA SGTPGQRVTI SCSGSSSNIG NNYVHWYQQL PGSAPKLLIY RNNQRPSGVP DRFSGSKSGT SGSLAISGLR SEDEADYYC ASWDDSLSGH WVFGGGTKVT VLGQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT PSKQSNNKYA ASSYLSLTPE QWKSHRSYSC QVTHEGSTVE KTVAPT

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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: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN 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 II (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 11.0 Å / Resolution method: OTHER / Number images used: 684

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Atomic model buiding 1

Initial model
PDB IDChain

5ire

chain_id: A, source_name: PDB, initial_model_type: experimental model

5ire

chain_id: B, source_name: PDB, initial_model_type: experimental model

5ire

chain_id: C, source_name: PDB, initial_model_type: experimental model

5ire

chain_id: D, source_name: PDB, initial_model_type: experimental model

5ire

chain_id: E, source_name: PDB, initial_model_type: experimental model

5ire

chain_id: F, source_name: PDB, initial_model_type: experimental model

5jep

chain_id: H, source_name: PDB, initial_model_type: experimental model

5jep

chain_id: L, source_name: PDB, initial_model_type: experimental model
Output model

PDB-6jfi:
The symmetric-reconstructed cryo-EM structure of Zika virus-FabZK2B10 complex

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