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Yorodumi- PDB-8wbc: CryoEM structure of non-structural protein 1 tetramer from dengue... -
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Basic information
| Entry | Database: PDB / ID: 8wbc | ||||||
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| Title | CryoEM structure of non-structural protein 1 tetramer from dengue virus type 4 | ||||||
Components | Genome polyprotein | ||||||
Keywords | VIRAL PROTEIN / flavivirus / non-structural protein 1 | ||||||
| Function / homology | Function and homology informationflavivirin / 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 / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport ...flavivirin / 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 / viral capsid / double-stranded RNA binding / nucleoside-triphosphate phosphatase / channel activity / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / methyltransferase cap1 activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / protein dimerization activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / serine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell nucleus / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / metal ion binding / membrane Similarity search - Function | ||||||
| Biological species | Dengue virus 4 Philippines/H241/1956 | ||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.03 Å | ||||||
Authors | Jiao, H.Z. / Pan, Q. / Hu, H.L. | ||||||
| Funding support | 1items
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Citation | Journal: Sci Adv / Year: 2024Title: The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution. Authors: Qi Pan / Haizhan Jiao / Wanqin Zhang / Qiang Chen / Geshu Zhang / Jianhai Yu / Wei Zhao / Hongli Hu / ![]() Abstract: Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on ...Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on several low-resolution structures, thus hindering the development of drugs and vaccines against flaviviruses. Here, we revealed that recombinant sNS1 from flaviviruses exists in a dynamic equilibrium of dimer-tetramer-hexamer states. Two DENV4 hexameric NS1 structures and several tetrameric NS1 structures from multiple flaviviruses were solved at atomic resolution by cryo-EM. The stacking of the tetrameric NS1 and hexameric NS1 is facilitated by the hydrophobic β-roll and connector domains. Additionally, a triacylglycerol molecule located within the central cavity may play a role in stabilizing the hexamer. Based on differentiated interactions between the dimeric NS1, two distinct hexamer models (head-to-head and side-to-side hexamer) and the step-by-step assembly mechanisms of NS1 dimer into hexamer were proposed. We believe that our study sheds light on the understanding of the NS1 oligomerization and contributes to NS1-based therapies. | ||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8wbc.cif.gz | 264.1 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8wbc.ent.gz | 214.5 KB | Display | PDB format |
| PDBx/mmJSON format | 8wbc.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8wbc_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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| Full document | 8wbc_full_validation.pdf.gz | 1.5 MB | Display | |
| Data in XML | 8wbc_validation.xml.gz | 47.8 KB | Display | |
| Data in CIF | 8wbc_validation.cif.gz | 71.2 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wb/8wbc ftp://data.pdbj.org/pub/pdb/validation_reports/wb/8wbc | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 37420MC ![]() 8wbbC ![]() 8wbdC ![]() 8wbeC ![]() 8wbfC ![]() 8wbgC ![]() 8wbhC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Protein | Mass: 40494.758 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Dengue virus 4 Philippines/H241/1956 / Strain: Philippines/H241/1956 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q58HT7Has protein modification | Y | |
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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 |
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Sample preparation
| Component | Name: dengue virus type 4 non-structural protein 1 tetramer / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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| Source (natural) | Organism: dengue virus type 4 |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE / Humidity: 100 % |
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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: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
| Image recording | Electron dose: 54 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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| 3D reconstruction | Resolution: 3.03 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 86204 / Symmetry type: POINT |
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Dengue virus 4 Philippines/H241/1956
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Homo sapiens (human)
FIELD EMISSION GUN