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Yorodumi- PDB-7dwt: Cryo-EM structure of Dengue virus serotype 1 strain WestPac 74 in... -
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-Basic information
Entry | Database: PDB / ID: 7dwt | ||||||||||||
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Title | Cryo-EM structure of Dengue virus serotype 1 strain WestPac 74 in complex with human antibody 1C19 Fab at 37 deg C (Class 1 particle) | ||||||||||||
Components |
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Keywords | VIRUS/IMMUNE SYSTEM / dengue virus / human antibody / dengue-Fab structure / VIRUS / VIRUS-IMMUNE SYSTEM complex | ||||||||||||
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 / channel activity / monoatomic ion transmembrane transport / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase ...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 / channel activity / monoatomic ion transmembrane transport / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 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 / protein dimerization activity / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / RNA-directed RNA polymerase / 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 / virion membrane / structural molecule activity / ATP hydrolysis activity / 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: 19 Å | ||||||||||||
Authors | Fibriansah, G. / Ng, T.S. / Kostyuchenko, V.A. / Shi, J. / Lok, S.M. | ||||||||||||
Funding support | Singapore, United States, 3items
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Citation | Journal: PLoS Pathog / Year: 2021 Title: Antibody affinity versus dengue morphology influences neutralization. Authors: Guntur Fibriansah / Elisa X Y Lim / Jan K Marzinek / Thiam-Seng Ng / Joanne L Tan / Roland G Huber / Xin-Ni Lim / Valerie S Y Chew / Victor A Kostyuchenko / Jian Shi / Ganesh S Anand / Peter ...Authors: Guntur Fibriansah / Elisa X Y Lim / Jan K Marzinek / Thiam-Seng Ng / Joanne L Tan / Roland G Huber / Xin-Ni Lim / Valerie S Y Chew / Victor A Kostyuchenko / Jian Shi / Ganesh S Anand / Peter J Bond / James E Crowe / Shee-Mei Lok / Abstract: Different strains within a dengue serotype (DENV1-4) can have smooth, or "bumpy" surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the ...Different strains within a dengue serotype (DENV1-4) can have smooth, or "bumpy" surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes. We mapped the 1C19 epitope to E protein domain II by hydrogen deuterium exchange mass spectrometry, cryoEM and molecular dynamics simulations, revealing that this epitope is likely partially hidden on the virus surface. We showed the antibody has high affinity for binding to recombinant DENV1 E proteins compared to those of DENV2, consistent with its strong neutralizing activities for all DENV1 strains tested regardless of their morphologies. This finding suggests that the antibody could out-compete E-to-E interaction for binding to its epitope. In contrast, for DENV2, HMAb 1C19 can only neutralize when the epitope becomes exposed on the bumpy-surfaced particle. Although HMAb 1C19 is not a suitable therapeutic candidate, this study with HMAb 1C19 shows the importance of choosing a high-affinity antibody that could neutralize diverse dengue virus morphologies for therapeutic purposes. | ||||||||||||
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 | 7dwt.cif.gz | 59 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7dwt.ent.gz | 32.6 KB | Display | PDB format |
PDBx/mmJSON format | 7dwt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7dwt_validation.pdf.gz | 789.8 KB | Display | wwPDB validaton report |
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Full document | 7dwt_full_validation.pdf.gz | 789.4 KB | Display | |
Data in XML | 7dwt_validation.xml.gz | 24.4 KB | Display | |
Data in CIF | 7dwt_validation.cif.gz | 35.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dw/7dwt ftp://data.pdbj.org/pub/pdb/validation_reports/dw/7dwt | HTTPS FTP |
-Related structure data
Related structure data | 30883MC 7dwuC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-Assembly
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 53910.871 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Dengue virus 1 / Strain: WestPac 74 / References: UniProt: P17763*PLUS #2: Antibody | | Mass: 13167.631 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) #3: Antibody | | Mass: 11584.849 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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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
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Source (natural) |
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Details of virus | Empty: NO / Enveloped: YES / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||||||
Buffer solution | pH: 8 Details: NTE buffer (12 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 Details: The purified virus was incubated with Fab 1C19 at 37 deg C for 30 min with a molar ratio of one Fab for every E-protein and followed by incubation at 4 deg C for 2 h. | ||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 18 e/Å2 / Film or detector model: FEI FALCON II (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4301 | ||||||||||||||||||||||||||||
Symmetry | Point symmetry: I (icosahedral) | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 19 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 1116 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||||||
Atomic model building |
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