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Yorodumi- EMDB-5935: Cryo-EM structure of Dengue virus serotype 3 in complex with huma... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-5935 | |||||||||
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Title | Cryo-EM structure of Dengue virus serotype 3 in complex with human antibody 5J7 Fab | |||||||||
Map data | Cryo-EM reconstruction of Dengue virus 3 in complex with human antibody 5J7 Fab | |||||||||
Sample |
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Keywords | dengue virus / human antibody / neutralization | |||||||||
Function / homology | Function and homology information host cell mitochondrion / 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 cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / : / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization ...host cell mitochondrion / 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 cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / : / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / double-stranded RNA binding / 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 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 / fusion of virus membrane with host endosome membrane / viral envelope / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / structural molecule activity / virion attachment to host cell / virion membrane / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Dengue virus 3 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 9.0 Å | |||||||||
Authors | Fibriansah G / Tan JL / Smith SA / de Alwis R / Ng T-S / Kostyuchenko VA / Kukkaro P / de Silva AM / Crowe Jr JE / Lok S-M | |||||||||
Citation | Journal: Nat Commun / Year: 2015 Title: A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins. Authors: Guntur Fibriansah / Joanne L Tan / Scott A Smith / Ruklanthi de Alwis / Thiam-Seng Ng / Victor A Kostyuchenko / Ramesh S Jadi / Petra Kukkaro / Aravinda M de Silva / James E Crowe / Shee-Mei Lok / Abstract: Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue ...Dengue virus (DENV) infects ~400 million people annually. There is no licensed vaccine or therapeutic drug. Only a small fraction of the total DENV-specific antibodies in a naturally occurring dengue infection consists of highly neutralizing antibodies. Here we show that the DENV-specific human monoclonal antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. The 9 Å resolution cryo-electron microscopy structure of the Fab 5J7-DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the antibody to fully coat the virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. Our study reveals a highly efficient and unusual mechanism of molecular recognition by an antibody. | |||||||||
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_5935.map.gz | 290.6 MB | EMDB map data format | |
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Header (meta data) | emd-5935-v30.xml emd-5935.xml | 13.2 KB 13.2 KB | Display Display | EMDB header |
Images | emd_5935.png | 394.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-5935 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-5935 | HTTPS FTP |
-Related structure data
Related structure data | 3j6uMC 5933C 5934C 3j6sC 3j6tC 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_5935.map.gz / Format: CCP4 / Size: 976.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Cryo-EM reconstruction of Dengue virus 3 in complex with human antibody 5J7 Fab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.37 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 3 complexed with human antibody 5J7 Fab
Entire | Name: Dengue virus 3 complexed with human antibody 5J7 Fab |
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Components |
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-Supramolecule #1000: Dengue virus 3 complexed with human antibody 5J7 Fab
Supramolecule | Name: Dengue virus 3 complexed with human antibody 5J7 Fab / type: sample / ID: 1000 / Number unique components: 2 |
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-Supramolecule #1: Dengue virus 3
Supramolecule | Name: Dengue virus 3 / type: virus / ID: 1 / NCBI-ID: 11069 / Sci species name: Dengue virus 3 / Sci species strain: D3/SG/05K863DK1/2005 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No |
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Host (natural) | Organism: Homo sapiens (human) / synonym: VERTEBRATES |
Host system | Organism: Aedes albopictus (Asian tiger mosquito) / Recombinant cell: C6/36 |
-Macromolecule #1: antibody 5J7 Fab
Macromolecule | Name: antibody 5J7 Fab / type: protein_or_peptide / ID: 1 / Recombinant expression: No / Database: NCBI |
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Source (natural) | Organism: Homo sapiens (human) / synonym: human |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 / Details: 10 mM Tris-HCl, pH 8.0, 120 mM NaCl, 1 mM EDTA |
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Grid | Details: ultra-thin carbon-coated lacey carbon grid |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 100 K / Instrument: FEI VITROBOT MARK IV Method: Blotted with filter paper for 2 seconds prior to snap freezing |
-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: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 4.2 µm / Nominal defocus min: 0.4 µm / Nominal magnification: 59000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Temperature | Average: 100 K |
Date | Mar 23, 2012 |
Image recording | Category: CCD / Film or detector model: FEI FALCON I (4k x 4k) / Digitization - Sampling interval: 14 µm / Number real images: 254 / Average electron dose: 18 e/Å2 / Bits/pixel: 16 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Details: each particle |
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Final reconstruction | Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 9.0 Å / Resolution method: OTHER / Software - Name: MPSA, EMAN, EMAN2 / Number images used: 970 |
Details | The particles were manually selected. |
-Atomic model buiding 1
Initial model | PDB ID: Chain - #0 - Chain ID: A / Chain - #1 - Chain ID: B / Chain - #2 - Chain ID: C / Chain - #3 - Chain ID: D / Chain - #4 - Chain ID: E / Chain - #5 - Chain ID: F |
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Software | Name: Chimera, Coot, NAMD/MDFF |
Details | Initially fitted in Chimera, model rebuilt in Coot, refined in NAMD/MDFF |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: real space correlation |
Output model | PDB-3j6u: |
-Atomic model buiding 2
Initial model | PDB ID: |
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Software | Name: Chimera, Coot, NAMD/MDFF |
Details | Initially fitted in Chimera, model rebuilt in Coot, refined in NAMD/MDFF |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: real space correlation |
Output model | PDB-3j6u: |
-Atomic model buiding 3
Initial model | PDB ID: |
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Software | Name: Chimera, Coot, NAMD/MDFF |
Details | Initially fitted in Chimera, model rebuilt in Coot, refined in NAMD/MDFF |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: real space correlation |
Output model | PDB-3j6u: |