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Open data
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Basic information
Entry | Database: PDB / ID: 6wcz | ||||||||||||||||||
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Title | CryoEM structure of full-length ZIKV NS5-hSTAT2 complex | ||||||||||||||||||
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![]() | IMMUNE SYSTEM / ZIKV NS5 / hSTAT2 / CryoEM | ||||||||||||||||||
Function / homology | ![]() ISGF3 complex / symbiont-mediated suppression of host interferon-mediated signaling pathway / Interleukin-20 family signaling / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / Regulation of IFNA/IFNB signaling / regulation of protein phosphorylation / flavivirin ...ISGF3 complex / symbiont-mediated suppression of host interferon-mediated signaling pathway / Interleukin-20 family signaling / negative regulation of type I interferon-mediated signaling pathway / type I interferon-mediated signaling pathway / regulation of mitochondrial fission / ubiquitin-like protein ligase binding / Regulation of IFNA/IFNB signaling / regulation of protein phosphorylation / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / cell surface receptor signaling pathway via JAK-STAT / 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 / ribonucleoside triphosphate phosphatase activity / defense response / Evasion by RSV of host interferon responses / response to peptide hormone / RNA polymerase II transcription regulator complex / Interferon alpha/beta signaling / viral capsid / double-stranded RNA binding / regulation of cell population proliferation / nucleoside-triphosphate phosphatase / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / symbiont-mediated suppression of host toll-like receptor signaling pathway / protein-macromolecule adaptor activity / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / defense response to virus / clathrin-dependent endocytosis of virus by host cell / Potential therapeutics for SARS / methyltransferase cap1 activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA helicase activity / protein dimerization activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host innate immune response / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA polymerase II cis-regulatory region sequence-specific DNA binding / symbiont entry into host cell / DNA-binding transcription factor activity / 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 / lipid binding / viral envelope / regulation of transcription by RNA polymerase II / chromatin / GTP binding / virion attachment to host cell / host cell nucleus / 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 / metal ion binding / identical protein binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | ||||||||||||||||||
![]() | 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 | ![]()
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![]() | ![]() 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. | ||||||||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 239 KB | Display | ![]() |
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PDB format | ![]() | 185.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 872.7 KB | Display | ![]() |
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Full document | ![]() | 898 KB | Display | |
Data in XML | ![]() | 39.5 KB | Display | |
Data in CIF | ![]() | 59.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 21618MC ![]() 6ux2C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() Production host: ![]() ![]() 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.) ![]() ![]() Production host: ![]() ![]() 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 |
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Sample preparation
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Molecular weight | Value: 141 kDa/nm / Experimental value: YES | ||||||||||||||||||||||||
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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 |
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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: ![]() |
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) |
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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 |