+Open data
-Basic information
Entry | Database: PDB / ID: 6wcz | ||||||||||||||||||
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Title | CryoEM structure of full-length ZIKV NS5-hSTAT2 complex | ||||||||||||||||||
Components |
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Keywords | IMMUNE SYSTEM / ZIKV NS5 / hSTAT2 / CryoEM | ||||||||||||||||||
Function / homology | Function and homology information ISGF3 complex / : / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / Interleukin-20 family signaling / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / cell surface receptor signaling pathway via JAK-STAT / flavivirin ...ISGF3 complex / : / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / Interleukin-20 family signaling / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / cell surface receptor signaling pathway via JAK-STAT / flavivirin / Regulation of IFNA/IFNB signaling / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / regulation of protein phosphorylation / Evasion by RSV of host interferon responses / response to peptide hormone / defense response / RNA polymerase II transcription regulator complex / viral capsid / double-stranded RNA binding / Interferon alpha/beta signaling / nucleoside-triphosphate phosphatase / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / regulation of cell population proliferation / symbiont-mediated suppression of host toll-like receptor signaling pathway / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / defense response to virus / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / Potential therapeutics for SARS / membrane => GO:0016020 / RNA helicase activity / host cell perinuclear region of cytoplasm / protein dimerization activity / host cell endoplasmic reticulum membrane / DNA-binding transcription factor activity, RNA polymerase II-specific / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / 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 / lipid binding / viral envelope / host cell nucleus / GTP binding / chromatin / regulation of transcription by RNA polymerase II / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / virion membrane / structural molecule activity / positive regulation of transcription by RNA polymerase II / ATP hydrolysis activity / proteolysis / extracellular region / nucleoplasm / ATP binding / identical protein binding / membrane / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) Zika virus | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||||||||||||||
Authors | Boxiao, W. / Stephanie, T. / Kang, Z. / Maria, T.S. / Jian, F. / Jiuwei, L. / Linfeng, G. / Wendan, R. / Yanxiang, C. / Ethan, C.V. ...Boxiao, W. / Stephanie, T. / Kang, Z. / Maria, T.S. / Jian, F. / Jiuwei, L. / Linfeng, G. / Wendan, R. / Yanxiang, C. / Ethan, C.V. / HeaJin, H. / Matthew, J.E. / Sean, E.O. / Adolfo, G.S. / Hong, Z. / Rong, H. / Jikui, S. | ||||||||||||||||||
Funding support | United States, 5items
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Citation | Journal: Nat Struct Mol Biol / Year: 2020 Title: Structural basis for STAT2 suppression by flavivirus NS5. Authors: Boxiao Wang / Stephanie Thurmond / Kang Zhou / Maria T Sánchez-Aparicio / Jian Fang / Jiuwei Lu / Linfeng Gao / Wendan Ren / Yanxiang Cui / Ethan C Veit / HeaJin Hong / Matthew J Evans / ...Authors: Boxiao Wang / Stephanie Thurmond / Kang Zhou / Maria T Sánchez-Aparicio / Jian Fang / Jiuwei Lu / Linfeng Gao / Wendan Ren / Yanxiang Cui / Ethan C Veit / HeaJin Hong / Matthew J Evans / Seán E O'Leary / Adolfo García-Sastre / Z Hong Zhou / Rong Hai / Jikui Song / Abstract: Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of ...Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9. Second, the NS5 RdRP domain also binds the amino-terminal domain of hSTAT2. Disruption of these ZIKV NS5-hSTAT2 interactions compromised NS5-mediated hSTAT2 degradation and interferon suppression, and viral infection under interferon-competent conditions. Taken together, these results clarify the mechanism underlying the functional antagonism of STAT2 by both ZIKV and DENV. | ||||||||||||||||||
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 | 6wcz.cif.gz | 239 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6wcz.ent.gz | 185.2 KB | Display | PDB format |
PDBx/mmJSON format | 6wcz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wcz_validation.pdf.gz | 872.7 KB | Display | wwPDB validaton report |
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Full document | 6wcz_full_validation.pdf.gz | 898 KB | Display | |
Data in XML | 6wcz_validation.xml.gz | 39.5 KB | Display | |
Data in CIF | 6wcz_validation.cif.gz | 59.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wc/6wcz ftp://data.pdbj.org/pub/pdb/validation_reports/wc/6wcz | HTTPS FTP |
-Related structure data
Related structure data | 21618MC 6ux2C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 98025.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: STAT2 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: P52630 | ||
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#2: Protein | Mass: 103118.703 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Zika virus / Gene: GP1, A2G93_72125gpGP1, A2G93_72126gpGP1 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: A0A2R4LVT4, UniProt: Q32ZE1*PLUS | ||
#3: Chemical | Has ligand of interest | N | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 141 kDa/nm / Experimental value: YES | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.5 / Details: 25 mM Tris-HCl, pH 7.5, 175 mM NaCl, 5 mM DTT | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER | ||||||||||||||||||||||||
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: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
Image recording | Electron dose: 48 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 118760 / Symmetry type: POINT |