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Yorodumi- EMDB-8548: A Human Antibody Against Zika Virus Crosslinks the E Protein to P... -
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-Basic information
Entry | Database: EMDB / ID: EMD-8548 | |||||||||||||||
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Title | A Human Antibody Against Zika Virus Crosslinks the E Protein to Prevent Infection | |||||||||||||||
Map data | Zika virus-antibody complex | |||||||||||||||
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 / 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 / membrane => GO:0016020 / 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 / 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 | Zika virus / Homo sapiens (human) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.2 Å | |||||||||||||||
Authors | Hasan SS / Miller A / Sapparapu G / Fernandez E / Klose T / Long F / Fokine A / Porta JC / Jiang W / Diamond MS ...Hasan SS / Miller A / Sapparapu G / Fernandez E / Klose T / Long F / Fokine A / Porta JC / Jiang W / Diamond MS / Crowe Jr JE / Kuhn RJ / Rossmann MG | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Nat Commun / Year: 2017 Title: A human antibody against Zika virus crosslinks the E protein to prevent infection. Authors: S Saif Hasan / Andrew Miller / Gopal Sapparapu / Estefania Fernandez / Thomas Klose / Feng Long / Andrei Fokine / Jason C Porta / Wen Jiang / Michael S Diamond / James E Crowe / Richard J ...Authors: S Saif Hasan / Andrew Miller / Gopal Sapparapu / Estefania Fernandez / Thomas Klose / Feng Long / Andrei Fokine / Jason C Porta / Wen Jiang / Michael S Diamond / James E Crowe / Richard J Kuhn / Michael G Rossmann / Abstract: The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. ...The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes. | |||||||||||||||
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_8548.map.gz | 218.1 MB | EMDB map data format | |
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Header (meta data) | emd-8548-v30.xml emd-8548.xml | 17.4 KB 17.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_8548_fsc.xml | 17.9 KB | Display | FSC data file |
Images | emd_8548.png | 207.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-8548 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8548 | HTTPS FTP |
-Related structure data
Related structure data | 5uhyMC 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_8548.map.gz / Format: CCP4 / Size: 307.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Zika virus-antibody complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.62 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Zika virus with ZIKV117 Fab
Entire | Name: Zika virus with ZIKV117 Fab |
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Components |
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-Supramolecule #1: Zika virus with ZIKV117 Fab
Supramolecule | Name: Zika virus with ZIKV117 Fab / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Zika virus |
-Macromolecule #1: ZV67 Fab chain 1
Macromolecule | Name: ZV67 Fab chain 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.658074 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: DIVMTQSQKF MSTSVGDRVS ITCKASQNVG TAVAWYQQKP GQSPKLLIYS ASNRYTGVPD RFTGSGSGTD FTLTISNMQS EDLADYFCQ QFSSYPYTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS ...String: DIVMTQSQKF MSTSVGDRVS ITCKASQNVG TAVAWYQQKP GQSPKLLIYS ASNRYTGVPD RFTGSGSGTD FTLTISNMQS EDLADYFCQ QFSSYPYTFG GGTKLEIKRA DAAPTVSIFP PSSEQLTSGG ASVVCFLNNF YPKDINVKWK IDGSERQNGV L NSWTDQDS KDSTYSMSST LTLTKDEYER HNSYTCEATH KTSTSPIVKS FNRNEC |
-Macromolecule #2: ZV67 Fab chain 2
Macromolecule | Name: ZV67 Fab chain 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.074842 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AQLQQSGTGL ARPGASVKLS CKASGYTFTS YGISWVTQRA GQGLEWIGVI YPRSGNTYYN EKFRGKATLT ADKSSSSAYM ELRGLTAED SAVYFCAREN YGSVYWGQGT TLTVSSAKTT APSVYPLAPV CGGTTGSSVT LGCLVKGYFP EPVTLTWNSG S LSSGVHTF ...String: AQLQQSGTGL ARPGASVKLS CKASGYTFTS YGISWVTQRA GQGLEWIGVI YPRSGNTYYN EKFRGKATLT ADKSSSSAYM ELRGLTAED SAVYFCAREN YGSVYWGQGT TLTVSSAKTT APSVYPLAPV CGGTTGSSVT LGCLVKGYFP EPVTLTWNSG S LSSGVHTF PALLQSGLYT LSSSVTVTSN TWPSQTITCN VAHPASSTKV DKKIEPRVPI |
-Macromolecule #3: envelope protein
Macromolecule | Name: envelope protein / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Zika virus |
Molecular weight | Theoretical: 43.123906 KDa |
Recombinant expression | Organism: Cricetinae gen. sp. (mammal) |
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 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Ted Pella 01824 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: LACEY / Details: no pretreatment | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Chamber temperature: 293 K / Instrument: GATAN CRYOPLUNGE 3 Details: 2.5 uL of sample was deposited on the carbon layer, with double-sided blotting applied twice for 5-6 seconds.. | ||||||||||||
Details | 1 mg/mL E protein |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal magnification: 18000 |
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) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Number grids imaged: 1 / Number real images: 1140 / Average exposure time: 11.0 sec. / Average electron dose: 32.6 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | PDB-5uhy: |