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Yorodumi- EMDB-21648: Enterovirus D68 in complex with human monoclonal antibody EV68-228 -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21648 | |||||||||||||||
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Title | Enterovirus D68 in complex with human monoclonal antibody EV68-228 | |||||||||||||||
Map data | Enterovirus D68 in complex with human monoclonal antibody EV68-228 | |||||||||||||||
Sample |
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Function / homology | Function and homology information picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / viral capsid ...picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / peptidase activity / host cell cytoplasm / RNA helicase activity / symbiont-mediated suppression of host innate immune response / symbiont entry into host cell / induction by virus of host autophagy / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / Enterovirus D68 | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||||||||
Authors | Fu J / Vogt MR / Klose T / Crowe JE / Rossmann MG / Kuhn RJ / Center for Structural Genomics of Infectious Diseases (CSGID) | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Sci Immunol / Year: 2020 Title: Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease. Authors: Matthew R Vogt / Jianing Fu / Nurgun Kose / Lauren E Williamson / Robin Bombardi / Ian Setliff / Ivelin S Georgiev / Thomas Klose / Michael G Rossmann / Yury A Bochkov / James E Gern / ...Authors: Matthew R Vogt / Jianing Fu / Nurgun Kose / Lauren E Williamson / Robin Bombardi / Ian Setliff / Ivelin S Georgiev / Thomas Klose / Michael G Rossmann / Yury A Bochkov / James E Gern / Richard J Kuhn / James E Crowe / Abstract: Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent ...Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68-reactive human monoclonal antibodies that recognize diverse antigenic variants from participants with prior infection. One potently neutralizing cross-reactive antibody, EV68-228, protected mice from respiratory and neurologic disease when given either before or after infection. Cryo-electron microscopy studies revealed that EV68-228 and another potently neutralizing antibody (EV68-159) bound around the fivefold or threefold axes of symmetry on virion particles, respectively. The structures suggest diverse mechanisms of action by these antibodies. The high potency and effectiveness observed in vivo suggest that antibodies are a mechanistic correlate of protection against AFM disease and are candidates for clinical use in humans with EV-D68 infection. | |||||||||||||||
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_21648.map.gz | 3.7 GB | EMDB map data format | |
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Header (meta data) | emd-21648-v30.xml emd-21648.xml | 21.7 KB 21.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_21648_fsc.xml | 36.1 KB | Display | FSC data file |
Images | emd_21648.png | 156.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21648 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21648 | HTTPS FTP |
-Validation report
Summary document | emd_21648_validation.pdf.gz | 165.4 KB | Display | EMDB validaton report |
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Full document | emd_21648_full_validation.pdf.gz | 165 KB | Display | |
Data in XML | emd_21648_validation.xml.gz | 499 B | Display | |
Data in CIF | emd_21648_validation.cif.gz | 373 B | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21648 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21648 | HTTPS FTP |
-Related structure data
Related structure data | 6wdtMC 6wdsC C: citing same article (ref.) M: atomic model generated by this map |
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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_21648.map.gz / Format: CCP4 / Size: 4 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Enterovirus D68 in complex with human monoclonal antibody EV68-228 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.662 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 : Enterovirus D68 in complex with human monoclonal antibody EV68-228
Entire | Name: Enterovirus D68 in complex with human monoclonal antibody EV68-228 |
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Components |
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-Supramolecule #1: Enterovirus D68 in complex with human monoclonal antibody EV68-228
Supramolecule | Name: Enterovirus D68 in complex with human monoclonal antibody EV68-228 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #3: human monoclonal antibody EV68-228
Supramolecule | Name: human monoclonal antibody EV68-228 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #5-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) / Recombinant cell: CHO |
-Supramolecule #2: Enterovirus D68
Supramolecule | Name: Enterovirus D68 / type: virus / ID: 2 / Parent: 1 / Macromolecule list: #1-#4 / NCBI-ID: 42789 / Sci species name: Enterovirus D68 / Sci species strain: US/MO/14-18047 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: No / Virus empty: No |
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Host system | Organism: Homo sapiens (human) / Recombinant cell: RD |
-Macromolecule #1: viral protein 1
Macromolecule | Name: viral protein 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus D68 / Strain: US/MO/14-18047 |
Molecular weight | Theoretical: 32.920309 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: IESIIKTATD TVKSEINAEL GVVPSLNAVE TGATSNTEPE EAIQTRTVIN QHGVSETLVE NFLSRAALVS KRSFEYKDHT SSTARADKN FFKWTINTRS FVQLRRKLEL FTYLRFDAEI TILTTVAVNG SGNNTYVGLP DLTLQAMFVP TGALTPEKQD S FHWQSGSN ...String: IESIIKTATD TVKSEINAEL GVVPSLNAVE TGATSNTEPE EAIQTRTVIN QHGVSETLVE NFLSRAALVS KRSFEYKDHT SSTARADKN FFKWTINTRS FVQLRRKLEL FTYLRFDAEI TILTTVAVNG SGNNTYVGLP DLTLQAMFVP TGALTPEKQD S FHWQSGSN ASVFFKISDP PARITIPFMC INSAYSVFYD GFAGFEKNGL YGINPADTIG NLCVRIVNEH QPVGFTVTVR VY MKPKHIK AWAPRPPRTL PYMSIANANY KGKERAPNAL SAIIGNRDSV KTMPHNIVNT |
-Macromolecule #2: viral protein 2
Macromolecule | Name: viral protein 2 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus D68 / Strain: US/MO/14-18047 |
Molecular weight | Theoretical: 27.567135 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SPSAEACGYS DRVLQLKLGN SAIVTQEAAN YCCAYGEWPN YLPDHEAVAI DKPTQPETAT DRFYTLKSVK WETGSTGWWW KLPDALNNI GMFGQNVQHH YLYRSGFLIH VQCNATKFHQ GALLVVAIPE HQRGAHNTNT SPGFDDIMKG EEGGTFNHPY V LDDGTSLA ...String: SPSAEACGYS DRVLQLKLGN SAIVTQEAAN YCCAYGEWPN YLPDHEAVAI DKPTQPETAT DRFYTLKSVK WETGSTGWWW KLPDALNNI GMFGQNVQHH YLYRSGFLIH VQCNATKFHQ GALLVVAIPE HQRGAHNTNT SPGFDDIMKG EEGGTFNHPY V LDDGTSLA CATIFPHQWI NLRTNNSATI VLPWMNAAPM DFPLRHNQWT LAIIPVVPLG TRTTSSMVPI TVSIAPMCCE FN GLRHAIT Q |
-Macromolecule #3: viral protein 3
Macromolecule | Name: viral protein 3 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus D68 / Strain: US/MO/14-18047 |
Molecular weight | Theoretical: 27.112814 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GVPTYLLPGS GQFLTTDDHS SAPALPCFNP TPEMHIPGQV RNMLEVVQVE SMMEINNTES AVGMERLKVD ISALTDVDQL LFNIPLDIQ LDGPLRNTLV GNISRYYTHW SGSLEMTFMF CGSFMAAGKL ILCYTPPGGS CPTTRETAML GTHIVWDFGL Q SSVTLIIP ...String: GVPTYLLPGS GQFLTTDDHS SAPALPCFNP TPEMHIPGQV RNMLEVVQVE SMMEINNTES AVGMERLKVD ISALTDVDQL LFNIPLDIQ LDGPLRNTLV GNISRYYTHW SGSLEMTFMF CGSFMAAGKL ILCYTPPGGS CPTTRETAML GTHIVWDFGL Q SSVTLIIP WISGSHYRMF NNDAKSTNAN VGYVTCFMQT NLIVPSESSD TCSLIGFIAA KDDFSLRLMR DSPDIGQLDH LH AAEAAYQ |
-Macromolecule #4: viral protein 4
Macromolecule | Name: viral protein 4 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus D68 / Strain: US/MO/14-18047 |
Molecular weight | Theoretical: 7.33696 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: GAQVTRQQTG THENANIATN GSHITYNQIN FYKDSYAASA SKQDFSQDPS KFTEPVVEGL KAGAPVLK |
-Macromolecule #5: EV68-228 heavy chain
Macromolecule | Name: EV68-228 heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 14.037602 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: QVQLQESGPG LVKPSETLSL TCTVSGYLIS NGYYWGWIRQ SPGKGLEWIG SIYYTRDTYY NWSLKSRITI SVDTSKKQFS LKLYSVTAA DTAVYYCVRH EGSCNDGSCY GSFVDNWGQG TLVTVSS |
-Macromolecule #6: EV68-228 light chain
Macromolecule | Name: EV68-228 light chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 11.354635 KDa |
Recombinant expression | Organism: Cricetulus griseus (Chinese hamster) |
Sequence | String: DIQMTQSPSS VSASVGDRVT LTCRASQDIS SWLAWYQQKP GKAPKLLIYA ASSLQSGVPS RFSGSGSGTH FTLTISSLQP EDFATYFCQ QADSFITFGG GTKVEIK |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Grid | Material: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: GATAN CRYOPLUNGE 3 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 462 / Average exposure time: 2.6 sec. / Average electron dose: 44.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |