+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35504 | |||||||||
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Title | Structure of Stimulator of interferon genes/ligand complex | |||||||||
Map data | ||||||||||
Sample |
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Keywords | complex / IMMUNE SYSTEM | |||||||||
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 | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Lu DF / Shang GJ | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35504.map.gz | 85.8 MB | EMDB map data format | |
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Header (meta data) | emd-35504-v30.xml emd-35504.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
Images | emd_35504.png | 97 KB | ||
Filedesc metadata | emd-35504.cif.gz | 5.5 KB | ||
Others | emd_35504_half_map_1.map.gz emd_35504_half_map_2.map.gz | 84 MB 84 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35504 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35504 | HTTPS FTP |
-Validation report
Summary document | emd_35504_validation.pdf.gz | 896.9 KB | Display | EMDB validaton report |
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Full document | emd_35504_full_validation.pdf.gz | 896.5 KB | Display | |
Data in XML | emd_35504_validation.xml.gz | 13 KB | Display | |
Data in CIF | emd_35504_validation.cif.gz | 15 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35504 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-35504 | HTTPS FTP |
-Related structure data
Related structure data | 8ik3MC 8ik0C 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_35504.map.gz / Format: CCP4 / Size: 91.1 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: 0.69 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_35504_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35504_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : complex of stimulator of interferon genes and ligand
Entire | Name: complex of stimulator of interferon genes and ligand |
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Components |
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-Supramolecule #1: complex of stimulator of interferon genes and ligand
Supramolecule | Name: complex of stimulator of interferon genes and ligand / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Stimulator of interferon genes protein,Immune protein Tsi3
Macromolecule | Name: Stimulator of interferon genes protein,Immune protein Tsi3 type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 58.152996 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MPHSSLHPSI PCPRGHGAQK AALVLLSACL VTLWGLGEPP EHTLRYLVLH LASLQLGLLL NGVCSLAEEL RHIHSRYRGS YWRTVRACL GCPLRRGALL LLSIYFYYSL PNAVGPPFTW MLALLGLSQA LNILLGLKGL APAEISAVCE KGNFNVAHGL A WSYYIGYL ...String: MPHSSLHPSI PCPRGHGAQK AALVLLSACL VTLWGLGEPP EHTLRYLVLH LASLQLGLLL NGVCSLAEEL RHIHSRYRGS YWRTVRACL GCPLRRGALL LLSIYFYYSL PNAVGPPFTW MLALLGLSQA LNILLGLKGL APAEISAVCE KGNFNVAHGL A WSYYIGYL RLILPELQAR IRTYNQHYNN LLRGAVSQRL YILLPLDCGV PDNLSMADPN IRFLDKLPQQ TGDRAGIKDR VY SNSIYEL LENGQRAGTC VLEYATPLQT LFAMSQYSQA GFSREDRLEQ AKLFCRTLED ILADAPESQN NCRLIAYQEP ADD SSFSLS QEVLRHLRQE EKEEVTVGSL KTSAVPSTST MSQEPELLIS GMEKPLPLRT DFSLEVLFQG PVDFDKTLTH PNGL VVERP VGFDARRSAE GFRFDEGGKL RNPRQLEVQR QDAPPPPDLA SRRLGDGEAR YKVEEDDGGS AGSEYRLWAA KPAGA RWIV VSASEQSEDG EPTFALAWAL LERARLQSSH HHHHHHH UniProtKB: Stimulator of interferon genes protein, Immune protein Tsi3 |
-Macromolecule #2: cGAMP
Macromolecule | Name: cGAMP / type: ligand / ID: 2 / Number of copies: 4 / Formula: 1SY |
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Molecular weight | Theoretical: 674.411 Da |
Chemical component information | ChemComp-1SY: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.5 / Details: 20mM HEPES, 150 mM NaCl, 1mM DTT |
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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 (6k x 4k) / Average electron dose: 60.0 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: 2.2 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 216426 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |