[English] 日本語
Yorodumi- EMDB-2442: Cryo-EM structure of Dengue virus serotype 1 complexed with Fab f... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-2442 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4 | |||||||||
Map data | Cryo-EM reconstruction of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4 | |||||||||
Sample |
| |||||||||
Keywords | dengue virus / cryo-EM / structure / E proteins / human antibody / antibody / neutralization | |||||||||
Function / homology | Function and homology information 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 / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / channel activity / double-stranded RNA binding / viral capsid / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell ...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 / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / ribonucleoside triphosphate phosphatase activity / channel activity / double-stranded RNA binding / viral capsid / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / protein dimerization activity / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / 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 / structural molecule activity / virion membrane / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Dengue virus 1 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.0 Å | |||||||||
Authors | Fibriansah G / Tan JL / de Alwis R / Smith SA / Ng T-S / Kostyuchenko VA / Ibarra KD / Harris E / de Silva A / Crowe JE / Lok S-M | |||||||||
Citation | Journal: EMBO Mol Med / Year: 2014 Title: A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. Authors: Guntur Fibriansah / Joanne L Tan / Scott A Smith / Adamberage R de Alwis / Thiam-Seng Ng / Victor A Kostyuchenko / Kristie D Ibarra / Jiaqi Wang / Eva Harris / Aravinda de Silva / James E Crowe / Shee-Mei Lok / Abstract: Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue ...Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 Å resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_2442.map.gz | 721 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-2442-v30.xml emd-2442.xml | 10.1 KB 10.1 KB | Display Display | EMDB header |
Images | emd_2442.tiff | 732.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-2442 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-2442 | HTTPS FTP |
-Validation report
Summary document | emd_2442_validation.pdf.gz | 342.1 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_2442_full_validation.pdf.gz | 341.2 KB | Display | |
Data in XML | emd_2442_validation.xml.gz | 8.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-2442 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-2442 | HTTPS FTP |
-Related structure data
Related structure data | 4c2iMC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_2442.map.gz / Format: CCP4 / Size: 976.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Cryo-EM reconstruction of Dengue virus serotype 1 complexed with Fab fragments of human antibody 1F4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : Dengue virus serotype 1 with Fab fragments of human monoclonal an...
Entire | Name: Dengue virus serotype 1 with Fab fragments of human monoclonal antibody 1F4 |
---|---|
Components |
|
-Supramolecule #1000: Dengue virus serotype 1 with Fab fragments of human monoclonal an...
Supramolecule | Name: Dengue virus serotype 1 with Fab fragments of human monoclonal antibody 1F4 type: sample / ID: 1000 Oligomeric state: 120 Fab molecules bind to one dengue virion Number unique components: 2 |
---|
-Supramolecule #1: Dengue virus 1
Supramolecule | Name: Dengue virus 1 / type: virus / ID: 1 / Details: strain PVP159 / NCBI-ID: 11053 / Sci species name: Dengue virus 1 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: Yes / Virus empty: No / Sci species serotype: 1 |
---|---|
Host (natural) | Organism: Homo sapiens (human) / synonym: VERTEBRATES |
Host system | Organism: Aedes albopictus (Asian tiger mosquito) / Recombinant cell: C6/36 |
-Macromolecule #1: Fab fragment of antibody 1F4
Macromolecule | Name: Fab fragment of antibody 1F4 / type: protein_or_peptide / ID: 1 / Recombinant expression: No |
---|---|
Source (natural) | Organism: Homo sapiens (human) / synonym: Human |
Molecular weight | Theoretical: 50 KDa |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 / Details: 12 mM Tris-HCl pH 8.0, 120 mM NaCl and 1 mM EDTA |
---|---|
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: blot with filter paper for 2 s before plunging |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Temperature | Average: 100 K |
Date | Sep 14, 2012 |
Image recording | Category: CCD / Film or detector model: FEI FALCON I (4k x 4k) / Number real images: 254 / Average electron dose: 17.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 4.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 47000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Details | The particles were selected manually. |
---|---|
CTF correction | Details: Each particle |
Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Algorithm: OTHER / Resolution.type: BY AUTHOR / Resolution: 6.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: EMAN, MPSA / Number images used: 10270 |