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- PDB-4uif: Cryo-EM structure of Dengue virus serotype 2 in complex with anti... -

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Entry
Database: PDB / ID: 4uif
TitleCryo-EM structure of Dengue virus serotype 2 in complex with antigen-binding fragments of human antibody 2D22
Components
  • ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
  • ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN
  • DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
  • DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
KeywordsVIRAL PROTEIN / DENGUE VIRUS / 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 / 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 / viral capsid / double-stranded RNA binding / channel activity / 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 / viral capsid / double-stranded RNA binding / channel activity / 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
Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C ...Flavivirus capsid protein C superfamily / Flavivirus non-structural protein NS2B / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M, flavivirus / Envelope glycoprotein M superfamily, flavivirus / Flavivirus envelope glycoprotein M / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flavivirus envelope glycoprotein E, stem/anchor domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / : / Flavivirus NS3 helicase, C-terminal helical domain / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / Immunoglobulin V-Type / Immunoglobulin V-set domain / Immunoglobulin V-set domain / : / helicase superfamily c-terminal domain / Immunoglobulin E-set / Immunoglobulin subtype / Immunoglobulin / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Helicase superfamily 1/2, ATP-binding domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / Immunoglobulin-like fold / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Genome polyprotein / Genome polyprotein / Genome polyprotein / IgG L chain
Similarity search - Component
Biological speciesDENGUE VIRUS 2
HOMO SAPIENS (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.5 Å
Model type detailsCA ATOMS ONLY, CHAIN A, C, E, B, D, F, G, I, K, H, J, L
AuthorsFibriansah, 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.
CitationJournal: 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
DepositionMar 30, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 15, 2015Provider: repository / Type: Initial release
Revision 1.1Aug 30, 2017Group: Data collection / Derived calculations / Category: em_imaging / em_software / pdbx_struct_assembly
Item: _em_imaging.nominal_defocus_max / _em_imaging.nominal_defocus_min ..._em_imaging.nominal_defocus_max / _em_imaging.nominal_defocus_min / _em_software.fitting_id / _em_software.image_processing_id / _pdbx_struct_assembly.details
Revision 1.2Feb 7, 2018Group: Database references / Structure summary / Category: citation / citation_author / struct
Item: _citation.journal_id_ISSN / _citation.page_last ..._citation.journal_id_ISSN / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.title / _citation_author.name / _struct.title
Revision 1.3May 8, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type

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Structure visualization

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  • Simplified surface model + fitted atomic model
  • EMDB-2967
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Assembly

Deposited unit
A: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
B: DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
C: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
D: DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
E: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
F: DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
G: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
H: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN
I: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
J: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN
K: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
L: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN


Theoretical massNumber of molelcules
Total (without water)264,79112
Polymers264,79112
Non-polymers00
Water00
1
A: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
B: DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
C: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
D: DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
E: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN
F: DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN
G: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
H: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN
I: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
J: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN
K: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN
L: ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN
x 60


Theoretical massNumber of molelcules
Total (without water)15,887,485720
Polymers15,887,485720
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_5551
point symmetry operation59
Noncrystallographic symmetry (NCS)NCS oper: (Code: given / Matrix: (1), (1), (1))

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Components

#1: Protein DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07 - ENVELOPE PROTEIN / Coordinate model: Cα atoms only


Mass: 54258.551 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) DENGUE VIRUS 2 / Strain: PVP94 07
Description: THE CELLS WERE INFECTED WITH DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07
Cell line (production host): C6/36 / Production host: AEDES ALBOPICTUS (Asian tiger mosquito) / References: UniProt: D6MQ38, UniProt: E0WXJ2*PLUS
#2: Protein DENGUE VIRUS SEROTYPE 2 STRAIN STRAIN PVP94 07 - MEMBRANE PROTEIN / Coordinate model: Cα atoms only


Mass: 8109.491 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) DENGUE VIRUS 2 / Strain: PVP94 07
Description: THE CELLS WERE INFECTED WITH DENGUE VIRUS SEROTYPE 2 STRAIN PVP94 07
Cell line (production host): C6/36 / Production host: AEDES ALBOPICTUS (Asian tiger mosquito) / References: UniProt: E0WXJ3, UniProt: E0WXJ2*PLUS
#3: Antibody ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - HEAVY CHAIN / Coordinate model: Cα atoms only


Mass: 13805.458 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) / Cell: MEMORY B-CELLS
#4: Antibody ANTIGEN-BINDING FRAGMENT OF HUMAN ANTIBODY 2D22 - LIGHT CHAIN / Coordinate model: Cα atoms only


Mass: 12090.306 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) / Cell: MEMORY B-CELLS / References: UniProt: S6BGD6

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: DENGUE VIRUS SEROTYPE 2 STRAIN PVP94-07 COMPLEXED WITH FAB FRAGMENTS OF HUMAN ANTIBODY 2D22.
Type: VIRUS
Buffer solutionName: 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
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: HOLEY CARBON
VitrificationInstrument: 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
MicroscopyModel: FEI TITAN KRIOS / Date: Feb 5, 2014
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal magnification: 47000 X / Nominal defocus max: 4700 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm
Specimen holderTemperature: 100 K
Image recordingElectron dose: 20 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k)
Image scansNum. digital images: 94

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Processing

EM software
IDNameVersionCategory
1MDFFmodel fitting
2NAMDmodel fitting
3UCSF Chimeramodel fitting
4EMAN13D reconstruction
5EMAN23D reconstruction
6MPSA3D reconstruction
CTF correctionDetails: EACH PARTICLE
SymmetryPoint symmetry: I (icosahedral)
3D reconstructionMethod: 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 buildingProtocol: FLEXIBLE FIT / Space: REAL / Target criteria: REAL-SPACE CORRELATION
Details: METHOD--FLEXIBLE FITTING USING MDFF-NAMD REFINEMENT PROTOCOL--CRYO-EM
Atomic model buildingPDB-ID: 3J27

3j27


Accession code: 3J27 / Source name: PDB / Type: experimental model
RefinementHighest resolution: 6.5 Å
Refinement stepCycle: LAST / Highest resolution: 6.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2394 0 0 0 2394

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