+Open data
-Basic information
Entry | Database: PDB / ID: 6nt5 | |||||||||||||||||||||
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Title | Cryo-EM structure of full-length human STING in the apo state | |||||||||||||||||||||
Components | Stimulator of interferon protein | |||||||||||||||||||||
Keywords | IMMUNE SYSTEM / ER / membrane / adaptor | |||||||||||||||||||||
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 / monoatomic ion transmembrane transport / regulation of inflammatory response / cytoplasmic vesicle / 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 / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||||||||||||||
Authors | Shang, G. / Zhang, C. / Chen, Z.J. / Bai, X. / Zhang, X. | |||||||||||||||||||||
Funding support | United States, 6items
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Citation | Journal: Nature / Year: 2019 Title: Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Authors: Guijun Shang / Conggang Zhang / Zhijian J Chen / Xiao-Chen Bai / Xuewu Zhang / Abstract: Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds ...Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS). STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain. The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP. However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180° rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses. | |||||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6nt5.cif.gz | 114 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nt5.ent.gz | 86 KB | Display | PDB format |
PDBx/mmJSON format | 6nt5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nt5_validation.pdf.gz | 855.1 KB | Display | wwPDB validaton report |
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Full document | 6nt5_full_validation.pdf.gz | 856.6 KB | Display | |
Data in XML | 6nt5_validation.xml.gz | 25.3 KB | Display | |
Data in CIF | 6nt5_validation.cif.gz | 35.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nt/6nt5 ftp://data.pdbj.org/pub/pdb/validation_reports/nt/6nt5 | HTTPS FTP |
-Related structure data
Related structure data | 0502MC 0503C 0504C 0505C 6nt6C 6nt7C 6nt8C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
#1: Protein | Mass: 42985.379 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: STING, LOC340061, hCG_1782396 / Cell line (production host): HEK293 GnTI- / Production host: Homo sapiens (human) / References: UniProt: A0A2R3XZB7, UniProt: Q86WV6*PLUS |
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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 |
-Sample preparation
Component | Name: full-length human STING / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 GnTI- |
Buffer solution | pH: 8 |
Specimen | Conc.: 4.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
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 |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
Image scans | Movie frames/image: 30 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 75479 / Symmetry type: POINT | ||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL |