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Yorodumi- EMDB-0506: Cryo-EM structure of the complex between human TBK1 and chicken STING -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0506 | |||||||||||||||||||||
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Title | Cryo-EM structure of the complex between human TBK1 and chicken STING | |||||||||||||||||||||
Map data | primary map | |||||||||||||||||||||
Sample |
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Keywords | ER / kinase / adaptor / IMMUNE SYSTEM | |||||||||||||||||||||
Function / homology | Function and homology information STING mediated induction of host immune responses / IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / proton channel activity / dendritic cell proliferation / regulation of type I interferon production / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding ...STING mediated induction of host immune responses / IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / proton channel activity / dendritic cell proliferation / regulation of type I interferon production / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / cGAS/STING signaling pathway / reticulophagy / TNFR1-induced proapoptotic signaling / toll-like receptor 4 signaling pathway / TRAF6 mediated IRF7 activation / cytoplasmic pattern recognition receptor signaling pathway / type I interferon-mediated signaling pathway / autophagosome membrane / antiviral innate immune response / positive regulation of macroautophagy / autophagosome assembly / autophagosome / positive regulation of type I interferon production / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of autophagy / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / TICAM1-dependent activation of IRF3/IRF7 / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / endoplasmic reticulum-Golgi intermediate compartment membrane / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Neutrophil degranulation / Negative regulators of DDX58/IFIH1 signaling / phosphoprotein binding / Regulation of TNFR1 signaling / peptidyl-threonine phosphorylation / DDX58/IFIH1-mediated induction of interferon-alpha/beta / response to virus / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of peptidyl-serine phosphorylation / protein complex oligomerization / TRAF3-dependent IRF activation pathway / cytoplasmic vesicle / peptidyl-serine phosphorylation / protein phosphatase binding / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / Potential therapeutics for SARS / nucleic acid binding / non-specific serine/threonine protein kinase / protein kinase activity / defense response to Gram-positive bacterium / inflammatory response / Golgi membrane / protein phosphorylation / negative regulation of gene expression / intracellular membrane-bounded organelle / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / perinuclear region of cytoplasm / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / identical protein binding / cytoplasm / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | Gallus gallus (chicken) / Homo sapiens (human) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||
Authors | Shang G / Zhang C | |||||||||||||||||||||
Funding support | United States, 6 items
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Citation | Journal: Nature / Year: 2019 Title: Structural basis of STING binding with and phosphorylation by TBK1. Authors: Conggang Zhang / Guijun Shang / Xiang Gui / Xuewu Zhang / Xiao-Chen Bai / Zhijian J Chen / Abstract: The invasion of mammalian cytoplasm by microbial DNA from infectious pathogens or by self DNA from the nucleus or mitochondria represents a danger signal that alerts the host immune system. Cyclic ...The invasion of mammalian cytoplasm by microbial DNA from infectious pathogens or by self DNA from the nucleus or mitochondria represents a danger signal that alerts the host immune system. Cyclic GMP-AMP synthase (cGAS) is a sensor of cytoplasmic DNA that activates the type-I interferon pathway. On binding to DNA, cGAS is activated to catalyse the synthesis of cyclic GMP-AMP (cGAMP) from GTP and ATP. cGAMP functions as a second messenger that binds to and activates stimulator of interferon genes (STING). STING then recruits and activates tank-binding kinase 1 (TBK1), which phosphorylates STING and the transcription factor IRF3 to induce type-I interferons and other cytokines. However, how cGAMP-bound STING activates TBK1 and IRF3 is not understood. Here we present the cryo-electron microscopy structure of human TBK1 in complex with cGAMP-bound, full-length chicken STING. The structure reveals that the C-terminal tail of STING adopts a β-strand-like conformation and inserts into a groove between the kinase domain of one TBK1 subunit and the scaffold and dimerization domain of the second subunit in the TBK1 dimer. In this binding mode, the phosphorylation site Ser366 in the STING tail cannot reach the kinase-domain active site of bound TBK1, which suggests that STING phosphorylation by TBK1 requires the oligomerization of both proteins. Mutational analyses validate the interaction mode between TBK1 and STING and support a model in which high-order oligomerization of STING and TBK1, induced by cGAMP, leads to STING phosphorylation by TBK1. | |||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_0506.map.gz | 3.6 MB | EMDB map data format | |
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Header (meta data) | emd-0506-v30.xml emd-0506.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_0506_fsc.xml | 7.9 KB | Display | FSC data file |
Images | emd_0506.png | 128.4 KB | ||
Filedesc metadata | emd-0506.cif.gz | 6.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0506 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0506 | HTTPS FTP |
-Validation report
Summary document | emd_0506_validation.pdf.gz | 387.3 KB | Display | EMDB validaton report |
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Full document | emd_0506_full_validation.pdf.gz | 386.9 KB | Display | |
Data in XML | emd_0506_validation.xml.gz | 10.1 KB | Display | |
Data in CIF | emd_0506_validation.cif.gz | 13 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0506 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0506 | HTTPS FTP |
-Related structure data
Related structure data | 6nt9MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_0506.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : full-length chicken STING and human TBK1
Entire | Name: full-length chicken STING and human TBK1 |
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Components |
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-Supramolecule #1: full-length chicken STING and human TBK1
Supramolecule | Name: full-length chicken STING and human TBK1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: STING
Supramolecule | Name: STING / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Gallus gallus (chicken) |
-Supramolecule #3: TBK1
Supramolecule | Name: TBK1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Serine/threonine-protein kinase TBK1
Macromolecule | Name: Serine/threonine-protein kinase TBK1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 85.316695 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLFAIKVF NNISFLRPVD VQMREFEVLK KLNHKNIVKL FAIEEETTTR HKVLIMEFC PCGSLYTVLE EPSNAYGLPE SEFLIVLRDV VGGMNHLREN GIVHRNIKPG NIMRVIGEDG QSVYKLTDFG A ARELEDDE ...String: MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLFAIKVF NNISFLRPVD VQMREFEVLK KLNHKNIVKL FAIEEETTTR HKVLIMEFC PCGSLYTVLE EPSNAYGLPE SEFLIVLRDV VGGMNHLREN GIVHRNIKPG NIMRVIGEDG QSVYKLTDFG A ARELEDDE QFVSLYGTEE YLHPDMYERA VLRKDHQKKY GATVDLWSIG VTFYHAATGS LPFRPFEGPR RNKEVMYKII TG KPSGAIS GVQKAENGPI DWSGDMPVSC SLSRGLQVLL TPVLANILEA DQEKCWGFDQ FFAETSDILH RMVIHVFSLQ QMT AHKIYI HSYNTATIFH ELVYKQTKII SSNQELIYEG RRLVLEPGRL AQHFPKTTEE NPIFVVSREP LNTIGLIYEK ISLP KVHPR YDLDGDASMA KAITGVVCYA CRIASTLLLY QELMRKGIRW LIELIKDDYN ETVHKKTEVV ITLDFCIRNI EKTVK VYEK LMKINLEAAE LGEISDIHTK LLRLSSSQGT IETSLQDIDS RLSPGGSLAD AWAHQEGTHP KDRNVEKLQV LLNCMT EIY YQFKKDKAER RLAYNEEQIH KFDKQKLYYH ATKAMTHFTD ECVKKYEAFL NKSEEWIRKM LHLRKQLLSL TNQCFDI EE EVSKYQEYTN ELQETLPQKM FTASSGIKHT MTPIYPSSNT LVEMTLGMKK LKEEMEGVVK ELAENNHILE RFGSLTMD G GLRNVDCLGI HRPDYKDDDD K UniProtKB: Serine/threonine-protein kinase TBK1 |
-Macromolecule #2: Stimulator of interferon genes protein
Macromolecule | Name: Stimulator of interferon genes protein / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Gallus gallus (chicken) |
Molecular weight | Theoretical: 44.20707 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MPQDPSTRSS PARLLIPEPR AGRARHAACV LLAVCFVVLF LSGEPLAPII RSVCTQLAAL QLGVLLKGCC CLAEEIFHLH SRHHGSLWQ VLCSCFPPRW YLALLLVGGS AYLDPPEDNG HSPRLALTLS CLCQLLVLAL GLQKLSAVEV SELTESSKKN V AHGLAWSY ...String: MPQDPSTRSS PARLLIPEPR AGRARHAACV LLAVCFVVLF LSGEPLAPII RSVCTQLAAL QLGVLLKGCC CLAEEIFHLH SRHHGSLWQ VLCSCFPPRW YLALLLVGGS AYLDPPEDNG HSPRLALTLS CLCQLLVLAL GLQKLSAVEV SELTESSKKN V AHGLAWSY YIGYLKVVLP RLKECMEELS RTNPMLRAHR DTWKLHILVP LGCDIWDDLE KADSNIQYLA DLPETILTRA GI KRRVYKH SLYVIRDKDN KLRPCVLEFA SPLQTLCAMS QDDCAAFSRE QRLEQARLFY RSLRDILGSS KECAGLYRLI AYE EPAEPE SHFLSGLILW HLQQQQREEY MVQEELPLGT SSVELSLQVS SSDLPQPLRS DCPGIHRPDY KDDDDK UniProtKB: Stimulator of interferon genes protein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4.5 mg/mL |
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Buffer | pH: 8 |
Grid | Pretreatment - Type: GLOW DISCHARGE / Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |