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- EMDB-2996: Cryo-EM structure of Dengue virus serotype 2 strain PVP94/07 comp... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-2996 | |||||||||
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Title | Cryo-EM structure of Dengue virus serotype 2 strain PVP94/07 complexed with human antibody 2D22 Fab at 37 degrees C | |||||||||
![]() | Reconstruction of Dengue virus serotype 2 strain PVP94/07 complexed with human antibody 2D22 Fab at 37 degrees C | |||||||||
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![]() | dengue virus / human antibody / cryo-EM / neutralization | |||||||||
Function / homology | ![]() symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / viral life cycle / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / host cell mitochondrion / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / viral life cycle / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / protein complex oligomerization / monoatomic ion channel activity / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / membrane => GO:0016020 / RNA helicase activity / host cell endoplasmic reticulum membrane / protein dimerization activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / induction by virus of host autophagy / serine-type endopeptidase activity / 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 / virion attachment to host cell / structural molecule activity / virion membrane / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.9 Å | |||||||||
![]() | Fibriansah G / Ibarra KD / Ng TS / Smith SA / Tan JL / Lim XN / Ooi JSG / Kostyuchenko VA / Wang J / de Silva AM ...Fibriansah G / Ibarra KD / Ng TS / Smith SA / Tan JL / Lim XN / Ooi JSG / Kostyuchenko VA / Wang J / de Silva AM / Harris E / Crowe JE / Lok SM | |||||||||
![]() | ![]() Title: DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers. Authors: Guntur Fibriansah / Kristie D Ibarra / Thiam-Seng Ng / Scott A Smith / Joanne L Tan / Xin-Ni Lim / Justin S G Ooi / Victor A Kostyuchenko / Jiaqi Wang / Aravinda M de Silva / Eva Harris / ...Authors: Guntur Fibriansah / Kristie D Ibarra / Thiam-Seng Ng / Scott A Smith / Joanne L Tan / Xin-Ni Lim / Justin S G Ooi / Victor A Kostyuchenko / Jiaqi Wang / Aravinda M de Silva / Eva Harris / James E Crowe / Shee-Mei Lok / ![]() ![]() Abstract: There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. ...There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)-specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo-electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 "locks" two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 160.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.4 KB 11.4 KB | Display Display | ![]() |
Images | ![]() | 399.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5a1zMC ![]() 2967C ![]() 2968C ![]() 2969C ![]() 2997C ![]() 2998C ![]() 2999C ![]() 4uifC ![]() 4uihC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Reconstruction of Dengue virus serotype 2 strain PVP94/07 complexed with human antibody 2D22 Fab at 37 degrees C | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.69 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Dengue virus serotype 2 strain PVP94/07 (a clinical isolate) comp...
Entire | Name: Dengue virus serotype 2 strain PVP94/07 (a clinical isolate) complexed with Fab fragments of human antibody 2D22. |
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Components |
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-Supramolecule #1000: Dengue virus serotype 2 strain PVP94/07 (a clinical isolate) comp...
Supramolecule | Name: Dengue virus serotype 2 strain PVP94/07 (a clinical isolate) complexed with Fab fragments of human antibody 2D22. type: sample / ID: 1000 Details: The complex was incubated at 37 degrees C for 30 min Number unique components: 2 |
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-Supramolecule #1: Dengue Virus serotype 2
Supramolecule | Name: Dengue Virus serotype 2 / type: virus / ID: 1 / Sci species name: Dengue Virus serotype 2 / Sci species strain: PVP94/07 / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No |
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Host (natural) | Organism: ![]() |
Host system | Organism: ![]() ![]() |
-Macromolecule #1: Antigen-binding fragment of human antibody 2D22
Macromolecule | Name: Antigen-binding fragment of human antibody 2D22 / type: protein_or_peptide / ID: 1 Details: 180 copies of Fab 2D22 molecule bind to virus surface Number of copies: 180 / Recombinant expression: No |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 50 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 / Details: 10 mM Tris-HCl pH 8.0, 120 mM NaCl and 1 mM EDTA |
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Grid | Details: ultra-thin carbon-coated lacey carbon grid |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV Method: blotted with filter paper for 2 seconds prior to snap freezing |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Date | Feb 27, 2014 |
Image recording | Category: CCD / Film or detector model: FEI FALCON II (4k x 4k) / Number real images: 177 / Average electron dose: 18 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 0.0042 µm / Nominal defocus min: 0.0011 µm / Nominal magnification: 47000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Details | The particles were manually selected |
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CTF correction | Details: Each particle |
Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 6.9 Å / Resolution method: OTHER / Software - Name: EMAN, EMAN2, MPSA / Number images used: 3435 |
-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, NAMD/MDFF |
Details | Initially fitted in Chimera and refined using NAMD/MDFF |
Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Target criteria: real-space correlation |
Output model | ![]() PDB-5a1z: |