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Yorodumi- EMDB-22818: Cryo-EM structure of Zika virus in complex with E protein cross-l... -
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-Basic information
Entry | Database: EMDB / ID: EMD-22818 | |||||||||
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Title | Cryo-EM structure of Zika virus in complex with E protein cross-linking human monoclonal antibody ADI30056 | |||||||||
Map data | ZIKV in complex with human monoclonal antibody ADI30056Zika virus | |||||||||
Sample |
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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 / 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 / negative regulation of innate immune response / ribonucleoside triphosphate phosphatase activity / 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 / membrane => GO:0016020 / molecular adaptor activity / host cell endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / protein dimerization 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 / centrosome / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / virion attachment to host cell / GTP binding / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
Authors | Sevvana M / Rogers TF / Miller AS / Long F / Klose T / Beutler N / Lai YC / Parren M / Walker LM / Buda G ...Sevvana M / Rogers TF / Miller AS / Long F / Klose T / Beutler N / Lai YC / Parren M / Walker LM / Buda G / Burton DR / Rossmann MG / Kuhn RJ | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Viruses / Year: 2020 Title: Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections. Authors: Madhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G ...Authors: Madhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G Rossmann / Richard J Kuhn / Abstract: Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We ...Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies. | |||||||||
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_22818.map.gz | 3.8 GB | EMDB map data format | |
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Header (meta data) | emd-22818-v30.xml emd-22818.xml | 22 KB 22 KB | Display Display | EMDB header |
Images | emd_22818.png | 222.6 KB | ||
Others | emd_22818_half_map_1.map.gz emd_22818_half_map_2.map.gz | 812 MB 812 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22818 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22818 | HTTPS FTP |
-Related structure data
Related structure data | 7kcrMC 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_22818.map.gz / Format: CCP4 / Size: 4 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | ZIKV in complex with human monoclonal antibody ADI30056 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: ZIKV in complex with human monoclonal antibody ADI30056 - Half Map 1
File | emd_22818_half_map_1.map | ||||||||||||
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Annotation | ZIKV in complex with human monoclonal antibody ADI30056 - Half Map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: ZIKV in complex with human monoclonal antibody ADI30056 - Half Map 2
File | emd_22818_half_map_2.map | ||||||||||||
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Annotation | ZIKV in complex with human monoclonal antibody ADI30056 - Half Map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Zika virus in complex with monoclonal antibody ADI30056
Entire | Name: Zika virus in complex with monoclonal antibody ADI30056 |
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Components |
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-Supramolecule #1: Zika virus in complex with monoclonal antibody ADI30056
Supramolecule | Name: Zika virus in complex with monoclonal antibody ADI30056 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 15 MDa |
-Supramolecule #3: monoclonal antibody ADI30056
Supramolecule | Name: monoclonal antibody ADI30056 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Scheffersomyces stipitis (fungus) |
-Supramolecule #2: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013
Supramolecule | Name: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 type: virus / ID: 2 / Parent: 1 / Macromolecule list: #3-#4 / NCBI-ID: 2043570 Sci species name: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No |
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Host (natural) | Organism: Homo sapiens (human) |
Host system | Organism: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 |
Virus shell | Shell ID: 1 / Name: Envelope protein shell / Diameter: 500.0 Å / T number (triangulation number): 3 |
-Macromolecule #1: ADI30056 Fab heavy chain variable region
Macromolecule | Name: ADI30056 Fab heavy chain variable region / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 13.467001 KDa |
Recombinant expression | Organism: Scheffersomyces stipitis (fungus) |
Sequence | String: EVQLLESGGG VVQPGGSLRL SCTASGFTFR NFGIHWVRQA PGKRLEWVAF IRYDGRNKYY ADSVKGRFIS SRDNSKNMVY LDMKSLRPE DTAIYHCAAD GEETSPGSFD YWGQGTLVTV SS |
-Macromolecule #2: ADI30056 Fab light chain variable region
Macromolecule | Name: ADI30056 Fab light chain variable region / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.385728 KDa |
Recombinant expression | Organism: Scheffersomyces stipitis (fungus) |
Sequence | String: DIVMTQTPSS LAASVGDSVT ITCRASESVS TVLNWYQHKP GKAPKLLIYA ASTLPSGVPS RFSGSGSGTD FTLSISSLQP EDFAIYYCQ QSYFSPRTFG GGTKVEIK |
-Macromolecule #3: envelope protein E
Macromolecule | Name: envelope protein E / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 |
Molecular weight | Theoretical: 54.186762 KDa |
Recombinant expression | Organism: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 |
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 LIFLSTA |
-Macromolecule #4: membrane protein M
Macromolecule | Name: membrane protein M / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 |
Molecular weight | Theoretical: 8.496883 KDa |
Recombinant expression | Organism: Zika virus ZIKV/H. sapiens/FrenchPolynesia/10087PF/2013 |
Sequence | String: AVTLPSHSTR KLQTRSQTWL ESREYTKHLI RVENWIFRNP GFALAAAAIA WLLGSSTSQK VIYLVMILLI APAYS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | 2D array |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 30.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Particle selection | Number selected: 165789 |
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CTF correction | Software - Name: CTFFIND (ver. 4) |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: jspr |
Final angle assignment | Type: PROJECTION MATCHING / Software - Name: jspr |
Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: jspr / Number images used: 22330 |