[English] 日本語
Yorodumi- PDB-4cau: THREE-DIMENSIONAL STRUCTURE OF DENGUE VIRUS SEROTYPE 1 COMPLEXED ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4cau | ||||||
---|---|---|---|---|---|---|---|
Title | THREE-DIMENSIONAL STRUCTURE OF DENGUE VIRUS SEROTYPE 1 COMPLEXED WITH 2 HMAB 14C10 FAB | ||||||
Components |
| ||||||
Keywords | VIRUS / FLAVIVIRUS / SEROTYPE 1 / MATURE VIRUS / ANTIBODIES / HUMAN ANTIBODIES / MONOCLONAL ANTIBODIES / HMAB | ||||||
Function / homology | Function and homology information symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / 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 ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / ribonucleoside triphosphate phosphatase activity / viral capsid / double-stranded RNA binding / 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 / protein dimerization activity / 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 / proteolysis / extracellular region / ATP binding / membrane / metal ion binding Similarity search - Function | ||||||
Biological species | DENGUE VIRUS 1 HOMO SAPIENS (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 7 Å | ||||||
Model type details | CA ATOMS ONLY, CHAIN A, B, C, D, E | ||||||
Authors | Teoh, E.P. / Kukkaro, P. / Teo, E.W. / Lim, A.P. / Tan, T.T. / Yip, A. / Schul, W. / Aung, M. / Kostyuchenko, V.A. / Leo, Y.S. ...Teoh, E.P. / Kukkaro, P. / Teo, E.W. / Lim, A.P. / Tan, T.T. / Yip, A. / Schul, W. / Aung, M. / Kostyuchenko, V.A. / Leo, Y.S. / Chan, S.H. / Smith, K.G. / Chan, A.H. / Zou, G. / Ooi, E.E. / Kemeny, D.M. / Tan, G.K. / Ng, J.K. / Ng, M.L. / Alonso, S. / Fisher, D. / Shi, P.Y. / Hanson, B.J. / Lok, S.M. / Macary, P.A. | ||||||
Citation | Journal: Sci Transl Med / Year: 2012 Title: The structural basis for serotype-specific neutralization of dengue virus by a human antibody. Authors: Ee Ping Teoh / Petra Kukkaro / En Wei Teo / Angeline P C Lim / Tze Tong Tan / Andy Yip / Wouter Schul / Myint Aung / Victor A Kostyuchenko / Yee Sin Leo / Soh Ha Chan / Kenneth G C Smith / ...Authors: Ee Ping Teoh / Petra Kukkaro / En Wei Teo / Angeline P C Lim / Tze Tong Tan / Andy Yip / Wouter Schul / Myint Aung / Victor A Kostyuchenko / Yee Sin Leo / Soh Ha Chan / Kenneth G C Smith / Annie Hoi Yi Chan / Gang Zou / Eng Eong Ooi / D Michael Kemeny / Grace K Tan / Jowin K W Ng / Mah Lee Ng / Sylvie Alonso / Dale Fisher / Pei-Yong Shi / Brendon J Hanson / Shee-Mei Lok / Paul A MacAry / Abstract: Dengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to ...Dengue virus (DENV) is a mosquito-borne flavivirus that affects 2.5 billion people worldwide. There are four dengue serotypes (DENV1 to DENV4), and infection with one elicits lifelong immunity to that serotype but offers only transient protection against the other serotypes. Identification of the protective determinants of the human antibody response to DENV is a vital requirement for the design and evaluation of future preventative therapies and treatments. Here, we describe the isolation of a neutralizing antibody from a DENV1-infected patient. The human antibody 14c10 (HM14c10) binds specifically to DENV1. HM14c10 neutralizes the virus principally by blocking virus attachment; at higher concentrations, a post-attachment step can also be inhibited. In vivo studies show that the HM14c10 antibody has antiviral activity at picomolar concentrations. A 7 Å resolution cryoelectron microscopy map of Fab fragments of HM14c10 in a complex with DENV1 shows targeting of a discontinuous epitope that spans the adjacent surface of envelope protein dimers. As found previously, a human antibody specific for the related West Nile virus binds to a similar quaternary structure, suggesting that this could be an immunodominant epitope. These findings provide a structural and molecular context for durable, serotype-specific immunity to DENV infection. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 4cau.cif.gz | 57.8 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4cau.ent.gz | 40.6 KB | Display | PDB format |
PDBx/mmJSON format | 4cau.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ca/4cau ftp://data.pdbj.org/pub/pdb/validation_reports/ca/4cau | HTTPS FTP |
---|
-Related structure data
Related structure data | 5268MC 3j05C M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
| x 60
2 |
|
3 |
| x 5
4 |
| x 6
5 |
|
Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 43750.883 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) DENGUE VIRUS 1 / Strain: 98901518 / References: UniProt: Q689G3 #2: Antibody | Mass: 25107.148 Da / Num. of mol.: 2 / Fragment: FAB / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) Sequence details | THE AUTHORS STATE THAT THERE ARE NO SEQUENCE CONFLICTS BETWEEN THE SEQUENCE IN THE PDB FILE AND ...THE AUTHORS STATE THAT THERE ARE NO SEQUENCE CONFLICTS BETWEEN THE SEQUENCE IN THE PDB FILE AND SEQUENCE DATABASE REFERENCE NCBI BAD42413 | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: COMPLEX OF FAB FRAGMENT OF HMAB 14C10 WITH DENGUE VIRUS SEROTYPE 1 Type: VIRUS |
---|---|
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: CARBON |
Vitrification | Instrument: FEI VITROBOT MARK I / Cryogen name: ETHANE / Details: LIQUID ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS / Date: Sep 27, 2010 |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 47000 X / Nominal defocus max: 4900 nm / Nominal defocus min: 760 nm / Cs: 2.7 mm |
Image recording | Electron dose: 16 e/Å2 / Film or detector model: GENERIC GATAN |
Radiation wavelength | Relative weight: 1 |
-Processing
EM software |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Details: INDIVIDUAL PARTICLES | ||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||
3D reconstruction | Method: CROSS-COMMON LINES / Resolution: 7 Å / Num. of particles: 2129 / Nominal pixel size: 1.9 Å / Actual pixel size: 1.9 Å / Details: PARTICLES WERE SELECTED MANUALLY / Symmetry type: POINT | ||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL / Details: METHOD--LOCAL CORRELATION | ||||||||||||
Atomic model building | PDB-ID: 3G7T | ||||||||||||
Refinement | Highest resolution: 7 Å | ||||||||||||
Refinement step | Cycle: LAST / Highest resolution: 7 Å
|