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Open data
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Basic information
Entry | Database: PDB / ID: 7r4h | ||||||
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Title | phospho-STING binding to adaptor protein complex-1 | ||||||
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![]() | IMMUNE SYSTEM / STING / innate immunity / TGN / AP-1 | ||||||
Function / homology | ![]() basolateral protein secretion / mitotic cleavage furrow ingression / endosome to melanosome transport / trans-Golgi Network Vesicle Budding / AP-1 adaptor complex / Lysosome Vesicle Biogenesis / platelet dense granule organization / regulation of receptor internalization / Glycosphingolipid transport / melanosome assembly ...basolateral protein secretion / mitotic cleavage furrow ingression / endosome to melanosome transport / trans-Golgi Network Vesicle Budding / AP-1 adaptor complex / Lysosome Vesicle Biogenesis / platelet dense granule organization / regulation of receptor internalization / Glycosphingolipid transport / melanosome assembly / STING complex / regulation of Arp2/3 complex-mediated actin nucleation / Intra-Golgi traffic / Golgi to vacuole transport / STAT6-mediated induction of chemokines / Synthesis of PIPs at the Golgi membrane / Golgi Associated Vesicle Biogenesis / protein localization to endoplasmic reticulum / serine/threonine protein kinase complex / proton channel activity / clathrin adaptor activity / 2',3'-cyclic GMP-AMP binding / STING mediated induction of host immune responses / MHC class II antigen presentation / cyclic-di-GMP binding / Nef Mediated CD4 Down-regulation / IRF3-mediated induction of type I IFN / dendritic spine organization / positive regulation of type I interferon-mediated signaling pathway / cGAS/STING signaling pathway / determination of left/right symmetry / reticulophagy / long-term synaptic depression / pattern recognition receptor signaling pathway / clathrin-coated vesicle / COPI-dependent Golgi-to-ER retrograde traffic / Lysosome Vesicle Biogenesis / cytoplasmic pattern recognition receptor signaling pathway / clathrin binding / Golgi Associated Vesicle Biogenesis / cellular response to exogenous dsRNA / cell leading edge / Synthesis of PIPs at the plasma membrane / autophagosome membrane / antiviral innate immune response / positive regulation of macroautophagy / cellular response to organic cyclic compound / autophagosome assembly / intracellular copper ion homeostasis / autophagosome / positive regulation of type I interferon production / cellular response to interferon-beta / protein targeting / COPI-mediated anterograde transport / signaling adaptor activity / clathrin-coated pit / vesicle-mediated transport / positive regulation of defense response to virus by host / MHC class II antigen presentation / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / Neutrophil degranulation / sarcomere / endoplasmic reticulum-Golgi intermediate compartment membrane / small monomeric GTPase / secretory granule membrane / trans-Golgi network membrane / Nef mediated downregulation of MHC class I complex cell surface expression / kidney development / intracellular protein transport / cytoplasmic vesicle membrane / trans-Golgi network / cellular response to virus / positive regulation of DNA-binding transcription factor activity / peroxisome / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / protein complex oligomerization / heart development / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / postsynaptic density / early endosome / endosome / neuron projection / protein domain specific binding / lysosomal membrane / Golgi membrane / intracellular membrane-bounded organelle / innate immune response / focal adhesion / GTPase activity / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / GTP binding Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.34 Å | ||||||
![]() | Xu, P. / Ablasser, A. | ||||||
Funding support | European Union, 1items
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![]() | ![]() Title: Clathrin-associated AP-1 controls termination of STING signalling. Authors: Ying Liu / Pengbiao Xu / Sophie Rivara / Chong Liu / Jonathan Ricci / Xuefeng Ren / James H Hurley / Andrea Ablasser / ![]() ![]() Abstract: Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate ...Stimulator of interferon genes (STING) functions downstream of cyclic GMP-AMP synthase in DNA sensing or as a direct receptor for bacterial cyclic dinucleotides and small molecules to activate immunity during infection, cancer and immunotherapy. Precise regulation of STING is essential to ensure balanced immune responses and prevent detrimental autoinflammation. After activation, STING, a transmembrane protein, traffics from the endoplasmic reticulum to the Golgi, where its phosphorylation by the protein kinase TBK1 enables signal transduction. The mechanism that ends STING signalling at the Golgi remains unknown. Here we show that adaptor protein complex 1 (AP-1) controls the termination of STING-dependent immune activation. We find that AP-1 sorts phosphorylated STING into clathrin-coated transport vesicles for delivery to the endolysosomal system, where STING is degraded. We identify a highly conserved dileucine motif in the cytosolic C-terminal tail (CTT) of STING that, together with TBK1-dependent CTT phosphorylation, dictates the AP-1 engagement of STING. A cryo-electron microscopy structure of AP-1 in complex with phosphorylated STING explains the enhanced recognition of TBK1-activated STING. We show that suppression of AP-1 exacerbates STING-induced immune responses. Our results reveal a structural mechanism of negative regulation of STING and establish that the initiation of signalling is inextricably associated with its termination to enable transient activation of immunity. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 407.8 KB | Display | ![]() |
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PDB format | ![]() | 329 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 66.9 KB | Display | |
Data in CIF | ![]() | 100.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 14312MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-AP-1 complex subunit ... , 4 types, 4 molecules BGMS
#1: Protein | Mass: 66008.422 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#3: Protein | Mass: 67399.242 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#5: Protein | Mass: 48606.730 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#6: Protein | Mass: 18321.338 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein / Protein/peptide , 2 types, 3 molecules CHL
#2: Protein | Mass: 18936.600 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein/peptide | | Mass: 1065.068 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: phospho-STING tail / Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 2 types, 4 molecules ![](data/chem/img/GTP.gif)
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#7: Chemical | #8: Chemical | |
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-Details
Has ligand of interest | 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: phospho-STING binding to adaptor protein complex-1 / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.4 / Details: PBS buffer | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
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 / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20rc2_4400: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.34 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 322238 / Symmetry type: POINT | ||||||||||||||||||||||||
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