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Yorodumi- EMDB-40953: Cryo-EM structure of DENV2 NS5 in complex with human STAT2 with t... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40953 | |||||||||
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Title | Cryo-EM structure of DENV2 NS5 in complex with human STAT2 with the N-terminal domain of STAT2 disordered | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Complex / IMMUNE SYSTEM-VIRAL PROTEIN complex | |||||||||
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 / host cell mitochondrion / Regulation of IFNA/IFNB signaling ...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 / host cell mitochondrion / Regulation of IFNA/IFNB signaling / 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 / channel activity / regulation of protein phosphorylation / Evasion by RSV of host interferon responses / response to peptide hormone / defense response / RNA polymerase II transcription regulator complex / monoatomic ion transmembrane transport / viral capsid / double-stranded RNA binding / Interferon alpha/beta signaling / regulation of cell population proliferation / 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 / RNA helicase activity / 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 / induction by virus of host autophagy / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / 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 / 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 / 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) / Dengue virus type 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.45 Å | |||||||||
Authors | Biswal M / Lu J / Song J | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Commun Biol / Year: 2024 Title: A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition. Authors: Mahamaya Biswal / Wangyuan Yao / Jiuwei Lu / Jianbin Chen / Juliet Morrison / Rong Hai / Jikui Song / Abstract: Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ...Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear. Here we report structure-function characterization of the DENV serotype 2 (DENV2) NS5-hSTAT2 complex. The MTase and RdRP domains of DENV2 NS5 form an extended conformation to interact with the coiled-coil and N-terminal domains of hSTAT2, thereby promoting hSTAT2 degradation in cells. Disruption of the extended conformation of DENV2/ZIKV NS5, but not the alternative compact state, impaired their hSTAT2 binding. Our comparative structural analysis of flavivirus NS5s further reveals a conserved protein-interaction platform with subtle amino-acid variations likely underpinning diverse IFN-suppression mechanisms. Together, this study uncovers a conformational selection mechanism underlying species-specific hSTAT2 inhibition by flavivirus NS5. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40953.map.gz | 126 MB | EMDB map data format | |
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Header (meta data) | emd-40953-v30.xml emd-40953.xml | 18.1 KB 18.1 KB | Display Display | EMDB header |
Images | emd_40953.png | 88.5 KB | ||
Filedesc metadata | emd-40953.cif.gz | 6.6 KB | ||
Others | emd_40953_additional_1.map.gz emd_40953_half_map_1.map.gz emd_40953_half_map_2.map.gz | 123 MB 226.7 MB 226.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40953 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40953 | HTTPS FTP |
-Validation report
Summary document | emd_40953_validation.pdf.gz | 888.5 KB | Display | EMDB validaton report |
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Full document | emd_40953_full_validation.pdf.gz | 888.1 KB | Display | |
Data in XML | emd_40953_validation.xml.gz | 15.9 KB | Display | |
Data in CIF | emd_40953_validation.cif.gz | 18.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40953 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40953 | HTTPS FTP |
-Related structure data
Related structure data | 8t13MC 8t12C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_40953.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.11 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_40953_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_40953_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_40953_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Complex of DENV2 NS5 with human STAT2
Entire | Name: Complex of DENV2 NS5 with human STAT2 |
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Components |
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-Supramolecule #1: Complex of DENV2 NS5 with human STAT2
Supramolecule | Name: Complex of DENV2 NS5 with human STAT2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Signal transducer and activator of transcription 2
Macromolecule | Name: Signal transducer and activator of transcription 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 98.025031 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: MAQWEMLQNL DSPFQDQLHQ LYSHSLLPVD IRQYLAVWIE DQNWQEAALG SDDSKATMLF FHFLDQLNYE CGRCSQDPES LLLQHNLRK FCRDIQPFSQ DPTQLAEMIF NLLLEEKRIL IQAQRAQLEQ GEPVLETPVE SQQHEIESRI LDLRAMMEKL V KSISQLKD ...String: MAQWEMLQNL DSPFQDQLHQ LYSHSLLPVD IRQYLAVWIE DQNWQEAALG SDDSKATMLF FHFLDQLNYE CGRCSQDPES LLLQHNLRK FCRDIQPFSQ DPTQLAEMIF NLLLEEKRIL IQAQRAQLEQ GEPVLETPVE SQQHEIESRI LDLRAMMEKL V KSISQLKD QQDVFCFRYK IQAKGKTPSL DPHQTKEQKI LQETLNELDK RRKEVLDASK ALLGRLTTLI ELLLPKLEEW KA QQQKACI RAPIDHGLEQ LETWFTAGAK LLFHLRQLLK ELKGLSCLVS YQDDPLTKGV DLRNAQVTEL LQRLLHRAFV VET QPCMPQ TPHRPLILKT GSKFTVRTRL LVRLQEGNES LTVEVSIDRN PPQLQGFRKF NILTSNQKTL TPEKGQSQGL IWDF GYLTL VEQRSGGSGK GSNKGPLGVT EELHIISFTV KYTYQGLKQE LKTDTLPVVI ISNMNQLSIA WASVLWFNLL SPNLQ NQQF FSNPPKAPWS LLGPALSWQF SSYVGRGLNS DQLSMLRNKL FGQNCRTEDP LLSWADFTKR ESPPGKLPFW TWLDKI LEL VHDHLKDLWN DGRIMGFVSR SQERRLLKKT MSGTFLLRFS ESSEGGITCS WVEHQDDDKV LIYSVQPYTK EVLQSLP LT EIIRHYQLLT EENIPENPLR FLYPRIPRDE AFGCYYQEKV NLQERRKYLK HRLIVVSNRQ VDELQQPLEL KPEPELES L ELELGLVPEP ELSLDLEPLL KAGLDLGPEL ESVLESTLEP VIEPTLCMVS QTVPEPDQGP VSQPVPEPDL PCDLRHLNT EPMEIFRNCV KIEEIMPNGD PLLAGQNTVD EVYVSRPSHF YTDGPLMPSD F UniProtKB: Signal transducer and activator of transcription 2 |
-Macromolecule #2: Non-structural protein 5
Macromolecule | Name: Non-structural protein 5 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Dengue virus type 2 |
Molecular weight | Theoretical: 103.264656 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: GTGNTGETLG EKWKNRLNAL GKSEFQIYKK SGIQEVDRTL AKEGIKRGET DHHAVSRGSA KLRWFVERNL VTPEGKVVDL GCGRGGWSY YCGGLKNVKE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFTPPEK CDTLLCDIGE SSPNPTVEAG R TLRVLNLV ...String: GTGNTGETLG EKWKNRLNAL GKSEFQIYKK SGIQEVDRTL AKEGIKRGET DHHAVSRGSA KLRWFVERNL VTPEGKVVDL GCGRGGWSY YCGGLKNVKE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFTPPEK CDTLLCDIGE SSPNPTVEAG R TLRVLNLV ENWLNNNTQF CIKVLNPYMP SVIEKMEALQ RKYGGALVRN PLSRNSTHEM YWVSNASGNI VSSVNMISRM LI NRFTMRH KKATYEPDVD LGSGTRNIGI ESETPNLDII GKRIEKIKQE HETSWHYDQD HPYKTWAYHG SYETKQTGSA SSM VNGVVR LLTKPWDIIP MVTQMAMTDT TPFGQQRVFK EKVDTRTQEP KEGTKKLMKI TAEWLWKELG KKKTPRMCTR EEFT RKVRS NAALGAIFTD ENKWKSAREA VEDSGFWELV DKERNLHLEG KCETCVYNMM GKREKKLGEF GKAKGSRAIW YMWLG ARFL EFEALGFLNE DHWFSRENSL SGVEGEGLHK LGYILRDVSK KEGGAMYADD TAGWDTRITL EDLKNEEMVT NHMEGE HKK LAEAIFKLTY QNKVVRVQRP TPRGTVMDII SRRDQRGSGQ VVTYGLNTFT NMEAQLIRQM EGEGVFKSIQ HLTVTEE IA VKNWLVRVGR ERLSRMAISG DDCVVKPLDD RFASALTALN DMGKVRKDIQ QWEPSRGWND WTQVPFCSHH FHELIMKD G RVLVVPCRNQ DELIGRARIS QGAGWSLRET ACLGKSYAQM WSLMYFHRRD LRLAANAICS AVPSHWVPTS RTTWSIHAT HEWMTTEDML TVWNRVWIQE NPWMEDKTPV ESWEEIPYLG KREDQWCGSL IGLTSRATWA KNIQTAINQV RSLIGNEEYT DYMPSMKRF RREEEEAGVL W UniProtKB: Genome polyprotein |
-Macromolecule #3: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 86928 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |