+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31678 | ||||||||||||
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Title | DENV2_NGC_Fab_C10 28degrees (2Fab:3E) | ||||||||||||
Map data | |||||||||||||
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 / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / 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 perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / 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 / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / structural molecule activity / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | ||||||||||||
Biological species | Dengue virus 2 Thailand/NGS-C/1944 / Homo sapiens (human) / Dengue virus type 2 (strain Thailand/NGS-C/1944) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Shu B / Zhang S / Victor AK / Ng TS / Lok SM | ||||||||||||
Funding support | Singapore, 3 items
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Citation | Journal: Cell / Year: 2021 Title: Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics. Authors: Xin-Xiang Lim / Bo Shu / Shuijun Zhang / Aaron W K Tan / Thiam-Seng Ng / Xin-Ni Lim / Valerie S-Y Chew / Jian Shi / Gavin R Screaton / Shee-Mei Lok / Ganesh S Anand / Abstract: The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 ...The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 (DENV2) particles by cryoelectron microscopy (cryo-EM) and amide hydrogen/deuterium exchange mass spectrometry (HDXMS) shows that Fab C10 binding decreases overall ZIKV particle dynamics, whereas with DENV2, the same Fab causes increased dynamics. Testing of different Fab C10:DENV2 E protein molar ratios revealed that, at higher Fab ratios, especially at saturated concentrations, the Fab enhanced viral dynamics (detected by HDXMS), and observation under cryo-EM showed increased numbers of distorted particles. Our results suggest that Fab C10 stabilizes ZIKV but that with DENV2 particles, high Fab C10 occupancy promotes E protein dimer conformational changes leading to overall increased particle dynamics and distortion of the viral surface. This is the first instance of a broadly neutralizing antibody eliciting virus-specific increases in whole virus particle dynamics. | ||||||||||||
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_31678.map.gz | 743.8 MB | EMDB map data format | |
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Header (meta data) | emd-31678-v30.xml emd-31678.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
Images | emd_31678.png | 211.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31678 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31678 | HTTPS FTP |
-Validation report
Summary document | emd_31678_validation.pdf.gz | 503.1 KB | Display | EMDB validaton report |
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Full document | emd_31678_full_validation.pdf.gz | 502.6 KB | Display | |
Data in XML | emd_31678_validation.xml.gz | 8.8 KB | Display | |
Data in CIF | emd_31678_validation.cif.gz | 10.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31678 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31678 | HTTPS FTP |
-Related structure data
Related structure data | 7v3gMC 7v3fC 7v3hC 7v3iC 7v3jC 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_31678.map.gz / Format: CCP4 / Size: 824 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.392 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 : Dengue virus 2 Thailand/NGS-C/1944_Fab_C10
Entire | Name: Dengue virus 2 Thailand/NGS-C/1944_Fab_C10 |
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Components |
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-Supramolecule #1: Dengue virus 2 Thailand/NGS-C/1944_Fab_C10
Supramolecule | Name: Dengue virus 2 Thailand/NGS-C/1944_Fab_C10 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Dengue virus 2 Thailand/NGS-C/1944 |
-Supramolecule #2: Dengue virus 2 Thailand/NGS-C/1944
Supramolecule | Name: Dengue virus 2 Thailand/NGS-C/1944 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: Fab_C10
Supramolecule | Name: Fab_C10 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #3-#4 |
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-Macromolecule #1: Envelope protein E
Macromolecule | Name: Envelope protein E / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Dengue virus type 2 (strain Thailand/NGS-C/1944) / Strain: Thailand/NGS-C/1944 |
Molecular weight | Theoretical: 54.363734 KDa |
Recombinant expression | Organism: Aedes albopictus C6/36 cell densovirus |
Sequence | String: MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIETEA KQPATLRKYC IEAKLTNTTT DSRCPTQGEP SLNEEQDKR FVCKHSMVDR GWGNGCGLFG KGGIVTCAMF TCKKNMKGKV VQPENLEYTI VITPHSGEEH AVGNDTGKHG K EIKITPQS ...String: MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIETEA KQPATLRKYC IEAKLTNTTT DSRCPTQGEP SLNEEQDKR FVCKHSMVDR GWGNGCGLFG KGGIVTCAMF TCKKNMKGKV VQPENLEYTI VITPHSGEEH AVGNDTGKHG K EIKITPQS SITEAELTGY GTVTMECSPR TGLDFNEMVL LQMENKAWLV HRQWFLDLPL PWLPGADTQG SNWIQKETLV TF KNPHAKK QDVVVLGSQE GAMHTALTGA TEIQMSSGNL LFTGHLKCRL RMDKLQLKGM SYSMCTGKFK VVKEIAETQH GTI VIRVQY EGDGSPCKIP FEIMDLEKRH VLGRLITVNP IVTEKDSPVN IEAEPPFGDS YIIIGVEPGQ LKLNWFKKGS SIGQ MIETT MRGAKRMAIL GDTAWDFGSL GGVFTSIGKA LHQVFGAIYG AAFSGVSWIM KILIGVIITW IGMNSRSTSL SVSLV LVGV VTLYLGVMVQ A |
-Macromolecule #2: Small envelope protein M
Macromolecule | Name: Small envelope protein M / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Dengue virus type 2 (strain Thailand/NGS-C/1944) / Strain: Thailand/NGS-C/1944 |
Molecular weight | Theoretical: 8.026385 KDa |
Recombinant expression | Organism: Aedes albopictus C6/36 cell densovirus |
Sequence | String: SVALVPHVGM GLETRTETWM SSEGAWKHAQ RIETWILRHP GFTIMAAILA YTIGTTHFQR ALIFILLTAV AP |
-Macromolecule #3: Fab_C10_light_chain
Macromolecule | Name: Fab_C10_light_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: 14.487058 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EVQLVESGAE VKKPGASVKV SCKASGYTFT SYAMHWVRQA PGQRLEWMGW INAGNGNTKY SQKFQDRVTI TRDTSASTAY MELSSLRSE DTAIYYCARD KVDDYGDYWF PTLWYFDYWG QGTLVTVS |
-Macromolecule #4: Fab_C10_heavy_chain
Macromolecule | Name: Fab_C10_heavy_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: 11.298362 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SALTQPASVS GSPGQSITIS CTGTSSDVGG FNYVSWFQQH PGKAPKLMLY DVTSRPSGVS SRFSGSKSGN TASLTISGLQ AEDEADYYC SSHTSRGTWV FGGGTKLTVL |
-Macromolecule #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 6 / Number of copies: 3 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-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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Sugar embedding | Material: ice |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 25.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 70534 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |