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Yorodumi- PDB-4uih: Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C ... -
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-Basic information
Entry | Database: PDB / ID: 4uih | ||||||
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Title | Cryo-EM structure of Dengue virus serotype 2 strain New Guinea-C complexed with human antibody 2D22 Fab at 37 degree C. The Fab molecules were added to the virus before 37 degree C incubation. | ||||||
Components |
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Keywords | VIRAL PROTEIN / DENGUE VIRUS / DENGUE SEROTYPE 2 / HUMAN ANTIBODY / CRYO-EM / NEUTRALIZATION | ||||||
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 HOMO SAPIENS (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 20 Å | ||||||
Model type details | CA ATOMS ONLY, CHAIN A, B, C, D, F, E, G | ||||||
Authors | 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, J.E. / Lok, S.-M. | ||||||
Citation | Journal: Science / Year: 2015 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 4uih.cif.gz | 65 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4uih.ent.gz | 37 KB | Display | PDB format |
PDBx/mmJSON format | 4uih.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4uih_validation.pdf.gz | 845.3 KB | Display | wwPDB validaton report |
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Full document | 4uih_full_validation.pdf.gz | 844.8 KB | Display | |
Data in XML | 4uih_validation.xml.gz | 27 KB | Display | |
Data in CIF | 4uih_validation.cif.gz | 39.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ui/4uih ftp://data.pdbj.org/pub/pdb/validation_reports/ui/4uih | HTTPS FTP |
-Related structure data
Related structure data | 2968MC 2967C 2969C 2996C 2997C 2998C 2999C 4uifC 5a1zC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 54363.734 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) DENGUE VIRUS 2 / Strain: NEW GUINEA-C Description: THE CELLS WERE INFECTED WITH DENGUE VIRUS SEROTYPE 2 STRAIN NEW GUINEA-C Cell line (production host): C6/36 / Production host: AEDES ALBOPICTUS (Asian tiger mosquito) References: UniProt: P14340, flavivirin, nucleoside-triphosphate phosphatase, RNA helicase, mRNA (guanine-N7)-methyltransferase, methyltransferase cap1, RNA-directed RNA polymerase #2: Antibody | Mass: 13805.458 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) / Cell: MEMORY B-CELLS #3: Antibody | Mass: 12090.306 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) / Cell: MEMORY B-CELLS |
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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 |
-Sample preparation
Component | Name: DENGUE VIRUS SEROTYPE 2 STRAIN NEW GUINEA-C COMPLEXED WITH FAB FRAGMENTS OF HUMAN ANTIBODY 2D22 AT 37 DEGREE C 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, |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS / Date: Jun 13, 2014 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 47000 X / Nominal defocus max: 3600 nm / Nominal defocus min: 1000 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: 168 |
-Processing
EM software |
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CTF correction | Details: EACH PARTICLE | ||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||
3D reconstruction | Method: CROSS-COMMON LINES / Resolution: 20 Å / Num. of particles: 4288 / Actual pixel size: 1.69 Å Details: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-2968. (DEPOSITION ID: 13278). Symmetry type: POINT | ||||||||||||||||||||
Atomic model building | Protocol: OTHER Details: METHOD--MANUAL FITTING USING O PROGRAM REFINEMENT PROTOCOL--CRYO-EM | ||||||||||||||||||||
Atomic model building | PDB-ID: 4UIF Accession code: 4UIF / Source name: PDB / Type: experimental model | ||||||||||||||||||||
Refinement | Highest resolution: 20 Å | ||||||||||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 20 Å
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