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- PDB-4uif: Cryo-EM structure of Dengue virus serotype 2 in complex with anti... -
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Basic information
Entry | Database: PDB / ID: 4uif | ||||||
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Title | Cryo-EM structure of Dengue virus serotype 2 in complex with antigen-binding fragments of human antibody 2D22 | ||||||
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![]() | VIRAL PROTEIN / DENGUE VIRUS / HUMAN ANTIBODY / CRYO-EM / NEUTRALIZATION | ||||||
Function / homology | ![]() 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 / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization ...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 / ribonucleoside triphosphate phosphatase activity / double-stranded RNA binding / viral capsid / nucleoside-triphosphate phosphatase / 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 / RNA helicase / induction by virus of host autophagy / viral RNA genome replication / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / endoplasmic reticulum membrane / structural molecule activity / virion membrane / proteolysis / extracellular region / ATP binding / membrane / nucleus / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.5 Å | ||||||
Model type details | CA ATOMS ONLY, CHAIN A, C, E, B, D, F, G, I, K, H, J, L | ||||||
![]() | Fibriansah, G. / Ibarra, K.D. / Ng, T.-S. / Smith, S.A. / Tan, J.L. / Lim, X.-N. / Ooi, J.S.G. / Kostyuchenko, V.A. / Wang, J. / de Silva, A.M. ...Fibriansah, G. / Ibarra, K.D. / Ng, T.-S. / Smith, S.A. / Tan, J.L. / Lim, X.-N. / Ooi, J.S.G. / Kostyuchenko, V.A. / Wang, J. / de Silva, A.M. / Harris, E. / Crowe Junior, J.E. / Lok, S.-M. | ||||||
![]() | ![]() 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 | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 81.3 KB | Display | ![]() |
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PDB format | ![]() | 49 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1008.9 KB | Display | ![]() |
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Full document | ![]() | 1008.5 KB | Display | |
Data in XML | ![]() | 34.2 KB | Display | |
Data in CIF | ![]() | 51.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 2967MC ![]() 2968C ![]() 2969C ![]() 2996C ![]() 2997C ![]() 2998C ![]() 2999C ![]() 4uihC ![]() 5a1zC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Noncrystallographic symmetry (NCS) | NCS oper: (Code: given / Matrix: (1), |
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Components
#1: Protein | Mass: 54258.551 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Description: THE CELLS WERE INFECTED WITH DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 Cell line (production host): C6/36 / Production host: ![]() ![]() #2: Protein | Mass: 8109.491 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Description: THE CELLS WERE INFECTED WITH DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 Cell line (production host): C6/36 / Production host: ![]() ![]() #3: Antibody | Mass: 13805.458 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) ![]() #4: Antibody | Mass: 12090.306 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94-07 COMPLEXED WITH FAB FRAGMENTS OF HUMAN ANTIBODY 2D22. Type: VIRUS |
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Buffer solution | Name: 10 MM TRIS-HCL PH 8.0, 120 MM NACL AND 1 MM EDTA / pH: 8 / Details: 10 MM TRIS-HCL PH 8.0, 120 MM NACL AND 1 MM EDTA |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: HOLEY CARBON |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE Details: VITRIFICATION 1 -- CRYOGEN- ETHANE, 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 imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS / Date: Feb 5, 2014 |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 47000 X / Nominal defocus max: 4700 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm |
Specimen holder | Temperature: 100 K |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
Image scans | Num. digital images: 94 |
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Processing
EM software |
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CTF correction | Details: EACH PARTICLE | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||
3D reconstruction | Method: CROSS-COMMON LINES / Resolution: 6.5 Å / Num. of particles: 2485 / Nominal pixel size: 1.688 Å Details: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-2967. (DEPOSITION ID: 13277). Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL / Target criteria: REAL-SPACE CORRELATION Details: METHOD--FLEXIBLE FITTING USING MDFF-NAMD REFINEMENT PROTOCOL--CRYO-EM | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 3J27 Accession code: 3J27 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||
Refinement | Highest resolution: 6.5 Å | ||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 6.5 Å
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