+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9542 | |||||||||
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Title | Zika virus complexed with a neutralizing antibody Z23-Fab | |||||||||
Map data | Zika virus in complex with a neutralizing antibody Z23-Fab,main map | |||||||||
Sample |
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Keywords | Zika 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 / negative regulation of innate immune response / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 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 / negative regulation of innate immune response / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 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 / molecular adaptor activity / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host innate immune response / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / symbiont entry into host cell / induction by virus of host autophagy / serine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / centrosome / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / host cell nucleus / virion attachment to host cell / GTP binding / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Zika virus / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 9.4 Å | |||||||||
Authors | Gao GF / Shi Y / Peng R | |||||||||
Funding support | China, 1 items
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Citation | Journal: 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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9542.map.gz | 378.7 MB | EMDB map data format | |
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Header (meta data) | emd-9542-v30.xml emd-9542.xml | 23.3 KB 23.3 KB | Display Display | EMDB header |
Images | emd_9542.png | 94.8 KB | ||
Filedesc metadata | emd-9542.cif.gz | 7 KB | ||
Others | emd_9542_half_map_1.map.gz emd_9542_half_map_2.map.gz | 380.7 MB 380.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9542 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9542 | HTTPS FTP |
-Validation report
Summary document | emd_9542_validation.pdf.gz | 857.3 KB | Display | EMDB validaton report |
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Full document | emd_9542_full_validation.pdf.gz | 856.8 KB | Display | |
Data in XML | emd_9542_validation.xml.gz | 18.2 KB | Display | |
Data in CIF | emd_9542_validation.cif.gz | 21.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9542 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9542 | HTTPS FTP |
-Related structure data
Related structure data | 5gzrMC 5gznC 5gzoC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9542.map.gz / Format: CCP4 / Size: 476.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Zika virus in complex with a neutralizing antibody Z23-Fab,main map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.58 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: half map 1
File | emd_9542_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 2
File | emd_9542_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Zika virus in complex with a neutralizing antibody Z23 Fab
Entire | Name: Zika virus in complex with a neutralizing antibody Z23 Fab |
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Components |
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-Supramolecule #1: Zika virus in complex with a neutralizing antibody Z23 Fab
Supramolecule | Name: 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
Supramolecule | Name: 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 |
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Source (natural) | Organism: Zika virus / Strain: ZIKA-SMGC-1 |
-Supramolecule #3: Neutralizing antibody Z23 Fab
Supramolecule | Name: Neutralizing antibody Z23 Fab / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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-Macromolecule #1: structural protein E
Macromolecule | Name: structural protein E / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Zika virus / Strain: isolate ZIKV_SMGC-1 |
Molecular weight | Theoretical: 54.444051 KDa |
Sequence | String: 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 |
-Macromolecule #2: strutural protein M
Macromolecule | Name: strutural protein M / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Zika virus / Strain: ZIKV_SMGC-1 |
Molecular weight | Theoretical: 8.496883 KDa |
Sequence | String: AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS UniProtKB: Genome polyprotein |
-Macromolecule #3: Z23 Fab heavy chain
Macromolecule | Name: Z23 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.516398 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Macromolecule #4: Z23 Fab light chain
Macromolecule | Name: Z23 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.416967 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: 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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 Component:
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Grid | Model: 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 | ||||||||||||
Vitrification | Cryogen 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. |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film 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 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 41139 |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | PDB-5gzr: |