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- EMDB-9542: Zika virus complexed with a neutralizing antibody Z23-Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-9542
TitleZika virus complexed with a neutralizing antibody Z23-Fab
Map dataZika virus in complex with a neutralizing antibody Z23-Fab,main map
Sample
  • Complex: Zika virus in complex with a neutralizing antibody Z23 Fab
    • Complex: Zika virus
      • Protein or peptide: structural protein EStructure
      • Protein or peptide: strutural protein M
    • Complex: Neutralizing antibody Z23 Fab
      • Protein or peptide: Z23 Fab heavy chain
      • Protein or peptide: Z23 Fab light chain
KeywordsZika virus / Neutralizing antibody / Single Particle Reconstruction / 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 / ribonucleoside triphosphate phosphatase activity / negative regulation of innate immune response / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / 4 iron, 4 sulfur cluster binding ...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 / ribonucleoside triphosphate phosphatase 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 / symbiont entry into host cell / 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
Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesZika virus / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 9.4 Å
AuthorsGao GF / Shi Y / Peng R
Funding support China, 1 items
OrganizationGrant numberCountry
China Ministry of Science and Technology Key Research and Development Program2016YFC1200300 China
CitationJournal: Sci Transl Med / Year: 2016
Title: Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus.
Authors: Qihui Wang / Huabing Yang / Xiaoqing Liu / Lianpan Dai / Tong Ma / Jianxun Qi / Gary Wong / Ruchao Peng / Sheng Liu / Junfu Li / Shihua Li / Jian Song / Jianying Liu / Jianhua He / Hui Yuan ...Authors: Qihui Wang / Huabing Yang / Xiaoqing Liu / Lianpan Dai / Tong Ma / Jianxun Qi / Gary Wong / Ruchao Peng / Sheng Liu / Junfu Li / Shihua Li / Jian Song / Jianying Liu / Jianhua He / Hui Yuan / Ying Xiong / Yong Liao / Jianhua Li / Jianping Yang / Zhou Tong / Bryan D Griffin / Yuhai Bi / Mifang Liang / Xiaoning Xu / Chuan Qin / Gong Cheng / Xinzheng Zhang / Peiyi Wang / Xiangguo Qiu / Gary Kobinger / Yi Shi / Jinghua Yan / George F Gao /
Abstract: The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and ...The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.
History
DepositionOct 1, 2016-
Header (metadata) releaseNov 30, 2016-
Map releaseNov 30, 2016-
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: 0.0085
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.0085
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-5gzr
  • Surface level: 0.0085
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-5gzr
  • 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_9542.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationZika virus in complex with a neutralizing antibody Z23-Fab,main map
Voxel sizeX=Y=Z: 1.58 Å
Density
Contour LevelBy AUTHOR: 0.0085 / Movie #1: 0.0085
Minimum - Maximum-0.006120061 - 0.02237205
Average (Standard dev.)0.00067709084 (±0.0030787727)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions500500500
Spacing500500500
CellA=B=C: 790.0 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.581.581.58
M x/y/z500500500
origin x/y/z0.0000.0000.000
length x/y/z790.000790.000790.000
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS500500500
D min/max/mean-0.0060.0220.001

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Supplemental data

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Half map: half map 1

Fileemd_9542_half_map_1.map
Annotationhalf map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: half map 2

Fileemd_9542_half_map_2.map
Annotationhalf map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Zika virus in complex with a neutralizing antibody Z23 Fab

EntireName: Zika virus in complex with a neutralizing antibody Z23 Fab
Components
  • Complex: Zika virus in complex with a neutralizing antibody Z23 Fab
    • Complex: Zika virus
      • Protein or peptide: structural protein EStructure
      • Protein or peptide: strutural protein M
    • Complex: Neutralizing antibody Z23 Fab
      • Protein or peptide: Z23 Fab heavy chain
      • Protein or peptide: Z23 Fab light chain

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Supramolecule #1: Zika virus in complex with a neutralizing antibody Z23 Fab

SupramoleculeName: Zika virus in complex with a neutralizing antibody Z23 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: Zika virus

SupramoleculeName: Zika virus / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2
Details: Zika virus strain ZIKA-SMGC-1 propagated in Aedes albopictus C6/36 cells
Source (natural)Organism: Zika virus / Strain: ZIKA-SMGC-1

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Supramolecule #3: Neutralizing antibody Z23 Fab

SupramoleculeName: Neutralizing antibody Z23 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4

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Macromolecule #1: structural protein E

MacromoleculeName: structural protein E / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Zika virus / Strain: isolate ZIKV_SMGC-1
Molecular weightTheoretical: 54.444051 KDa
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 LIFLSTAVSA

UniProtKB: Genome polyprotein

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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
Source (natural)Organism: Zika virus / Strain: ZIKV_SMGC-1
Molecular weightTheoretical: 8.496883 KDa
SequenceString:
AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS

UniProtKB: Genome polyprotein

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Macromolecule #3: Z23 Fab heavy chain

MacromoleculeName: Z23 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.516398 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGR INPNSGGTNY AQKFEGRVTM TRDTSISTAY MELSRLRSD DTAVYYCART GIAAAGFVFD YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String:
QVQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGR INPNSGGTNY AQKFEGRVTM TRDTSISTAY MELSRLRSD DTAVYYCART GIAAAGFVFD YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEP

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Macromolecule #4: Z23 Fab light chain

MacromoleculeName: Z23 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.416967 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIVMTQSPAT LSVSPGERAT LSCRASQSVI SNLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWWTFGQ GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK ...String:
DIVMTQSPAT LSVSPGERAT LSCRASQSVI SNLAWYQQKP GQAPRLLIYG ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWWTFGQ GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ E SVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ GLSSPVTKSF NRGECS

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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
Component:
ConcentrationFormulaName
12.0 mMTris-HClTrisTris-HClTris
120.0 mMNaClSodium chlorideSodium Chloride
1.0 mMEDTAEthylenediaminetetraacetic acidEthylenediaminetetraacetic acid
GridModel: Zhongjikeyi ultra-thin carbon-coated copper grid / Material: COPPER / Mesh: 230 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 101.325 kPa
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
Details: 3 uL Zika virus-Z23 Fab complex sample was transferred onto a glow-discharged ultra-thin carbon-coated copper grid (Purchased from Zhongjingkeyi Company, China) followed by 60s waiting and ...Details: 3 uL Zika virus-Z23 Fab complex sample was transferred onto a glow-discharged ultra-thin carbon-coated copper grid (Purchased from Zhongjingkeyi Company, China) followed by 60s waiting and blotted for 2s with filter paper before plugging into liquid ethane using the FEI Vitrobot Mark IV.

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 41139
Sample stageCooling holder cryogen: NITROGEN
Image recordingFilm or detector model: DIRECT ELECTRON DE-20 (5k x 3k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 566 / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 17024
Startup modelType of model: EMDB MAP
EMDB ID:

Details: Low-pass filtered to 60 angstrom
Initial angle assignmentType: RANDOM ASSIGNMENT / Software - Name: RELION (ver. 1.4)
Final 3D classificationSoftware - Name: RELION (ver. 1.4)
Final angle assignmentType: OTHER / Software - Name: RELION (ver. 1.4)
Final reconstructionApplied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 9.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 1.4) / Number images used: 3369

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Atomic model buiding 1

RefinementProtocol: RIGID BODY FIT
Output model

PDB-5gzr:
Zika virus E protein complexed with a neutralizing antibody Z23-Fab

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