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Open data
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Basic information
| Entry | Database: PDB / ID: 9dan | ||||||||||||||||||||||||
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| Title | STING oligomer bound to PI(4,5)P2 | ||||||||||||||||||||||||
Components | Stimulator of interferon genes protein | ||||||||||||||||||||||||
Keywords | SIGNALING PROTEIN/ACTIVATOR / STING / lipid / oligomerization / SIGNALING PROTEIN / SIGNALING PROTEIN-ACTIVATOR complex | ||||||||||||||||||||||||
| Function / homology | Function and homology informationSTING complex / STAT6-mediated induction of chemokines / serine/threonine protein kinase complex / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / proton channel activity ...STING complex / STAT6-mediated induction of chemokines / serine/threonine protein kinase complex / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / proton channel activity / reticulophagy / cGAS/STING signaling pathway / pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / cytoplasmic pattern recognition receptor signaling pathway / protein complex oligomerization / autophagosome membrane / positive regulation of macroautophagy / autophagosome assembly / cellular response to interferon-beta / positive regulation of defense response to virus by host / positive regulation of type I interferon production / endoplasmic reticulum-Golgi intermediate compartment membrane / signaling adaptor activity / activation of innate immune response / positive regulation of interferon-beta production / autophagosome / secretory granule membrane / Regulation of innate immune responses to cytosolic DNA / cytoplasmic vesicle membrane / antiviral innate immune response / protein serine/threonine kinase binding / SARS-CoV-1 activates/modulates innate immune responses / peroxisome / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / transcription coactivator activity / endosome / cilium / ciliary basal body / Golgi membrane / innate immune response / Neutrophil degranulation / ubiquitin protein ligase binding / endoplasmic reticulum membrane / protein kinase binding / perinuclear region of cytoplasm / SARS-CoV-2 activates/modulates innate and adaptive immune responses / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / plasma membrane / cytosol Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||||||||||||||||||||
Authors | Li, J. / Zhang, X. / Bai, X. | ||||||||||||||||||||||||
| Funding support | United States, 3items
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Citation | Journal: Nature / Year: 2026Title: Regulation of STING activation by phosphoinositide and cholesterol. Authors: Jie Li / Jay Xiaojun Tan / Zhijian J Chen / Xuewu Zhang / Xiao-Chen Bai / ![]() Abstract: Stimulator of interferon genes (STING) is an essential adaptor in the cytosolic DNA-sensing innate immune pathway. STING is activated by cyclic GMP-AMP (cGAMP) produced by the DNA sensor cGAMP ...Stimulator of interferon genes (STING) is an essential adaptor in the cytosolic DNA-sensing innate immune pathway. STING is activated by cyclic GMP-AMP (cGAMP) produced by the DNA sensor cGAMP synthase (cGAS). cGAMP-induced high-order oligomerization and translocation of STING from the endoplasmic reticulum to the Golgi and post-Golgi vesicles are critical for STING activation. Other studies have shown that phosphatidylinositol phosphates (PtdInsPs) and cholesterol also have important roles in STING activation, but the underlying mechanisms remain unclear. Here we demonstrate that cGAMP-induced high-order oligomerization of STING is enhanced strongly by phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P and PtdIns(4,5)P, and by PtdIns4P to a lesser extent. Our cryo-electron microscopy structures reveal that PtdInsPs together with cholesterol bind at the interface between STING dimers, directly promoting the high-order oligomerization. The structures also provide an explanation for the preference of the STING oligomer to different PtdInsPs. Mutational and biochemical analyses confirm the binding modes of PtdInsPs and cholesterol and their roles in STING activation. Our findings shed light on the regulatory mechanisms of STING mediated by specific lipids, which may underlie the role of intracellular trafficking in dictating STING signalling. | ||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9dan.cif.gz | 493.6 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9dan.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9dan.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/da/9dan ftp://data.pdbj.org/pub/pdb/validation_reports/da/9dan | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 46694MC ![]() 9datC ![]() 9davC ![]() 9dawC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Protein | Mass: 39553.398 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: STING1, ERIS, MITA, TMEM173 / Production host: Homo sapiens (human) / References: UniProt: Q86WV6#2: Chemical | #3: Chemical | Mass: 1023.066 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C45H85O19P3 / Feature type: SUBJECT OF INVESTIGATION #4: Chemical | #5: Chemical | Has ligand of interest | Y | Has protein modification | N | |
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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: STING oligomer bound to its ligand cGAMP, a synthetic activator named STG2, Cholesteryl hemisuccinate and PI(4,5)P2 Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 1.2 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 242771 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)
United States, 3items
Citation






PDBj








FIELD EMISSION GUN