+Open data
-Basic information
Entry | Database: PDB / ID: 8ik3 | ||||||
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Title | Structure of Stimulator of interferon genes/ligand complex | ||||||
Components | Stimulator of interferon genes protein,Immune protein Tsi3 | ||||||
Keywords | IMMUNE SYSTEM / complex | ||||||
Function / homology | Function and homology information STING complex / STING mediated induction of host immune responses / STAT6-mediated induction of chemokines / serine/threonine protein kinase complex / protein localization to endoplasmic reticulum / proton channel activity / 2',3'-cyclic GMP-AMP binding / pattern recognition receptor signaling pathway / cGAS/STING signaling pathway / IRF3-mediated induction of type I IFN ...STING complex / STING mediated induction of host immune responses / STAT6-mediated induction of chemokines / serine/threonine protein kinase complex / protein localization to endoplasmic reticulum / proton channel activity / 2',3'-cyclic GMP-AMP binding / pattern recognition receptor signaling pathway / cGAS/STING signaling pathway / IRF3-mediated induction of type I IFN / cyclic-di-GMP binding / positive regulation of type I interferon-mediated signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / reticulophagy / cellular response to exogenous dsRNA / cellular response to organic cyclic compound / positive regulation of type I interferon production / autophagosome membrane / positive regulation of macroautophagy / autophagosome assembly / cellular response to interferon-beta / positive regulation of defense response to virus by host / signaling adaptor activity / activation of innate immune response / antiviral innate immune response / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of interferon-beta production / autophagosome / protein complex oligomerization / Regulation of innate immune responses to cytosolic DNA / secretory granule membrane / positive regulation of DNA-binding transcription factor activity / cytoplasmic vesicle membrane / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / peroxisome / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / endosome / Golgi membrane / innate immune response / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / protein kinase binding / 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 / identical protein binding / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
Authors | Lu, D.F. / Shang, G.J. | ||||||
Funding support | China, 1items
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Citation | Journal: Mol Cell / Year: 2023 Title: The mechanism of STING autoinhibition and activation. Authors: Sheng Liu / Bo Yang / Yingxiang Hou / Kaige Cui / Xiaozhu Yang / Xiaoxiong Li / Lianwan Chen / Shichao Liu / Zhichao Zhang / Yuanyuan Jia / Yufeng Xie / Ying Xue / Xiaomei Li / Bingxue Yan / ...Authors: Sheng Liu / Bo Yang / Yingxiang Hou / Kaige Cui / Xiaozhu Yang / Xiaoxiong Li / Lianwan Chen / Shichao Liu / Zhichao Zhang / Yuanyuan Jia / Yufeng Xie / Ying Xue / Xiaomei Li / Bingxue Yan / Changxin Wu / Wen Deng / Jianxun Qi / Defen Lu / George F Gao / Peiyi Wang / Guijun Shang / Abstract: 2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the ...2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ik3.cif.gz | 470.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ik3.ent.gz | 384.5 KB | Display | PDB format |
PDBx/mmJSON format | 8ik3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ik3_validation.pdf.gz | 1.9 MB | Display | wwPDB validaton report |
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Full document | 8ik3_full_validation.pdf.gz | 2 MB | Display | |
Data in XML | 8ik3_validation.xml.gz | 78.5 KB | Display | |
Data in CIF | 8ik3_validation.cif.gz | 112.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ik/8ik3 ftp://data.pdbj.org/pub/pdb/validation_reports/ik/8ik3 | HTTPS FTP |
-Related structure data
Related structure data | 35504MC 8ik0C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 58152.996 Da / Num. of mol.: 8 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: STING1, ERIS, MITA, STING, TMEM173, tsi3, PA3485 / Production host: Homo sapiens (human) / References: UniProt: Q86WV6, UniProt: Q9HYC4 #2: Chemical | ChemComp-1SY / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: complex of stimulator of interferon genes and ligand / Type: COMPLEX / Entity ID: #1 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 / Details: 20mM HEPES, 150 mM NaCl, 1mM DTT |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: 2200 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 216426 / Symmetry type: POINT | ||||||||||||||||||||||||
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