+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-0503 | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of full-length chicken STING in the apo state | |||||||||||||||||||||
![]() | primary map | |||||||||||||||||||||
![]() |
| |||||||||||||||||||||
![]() | ER / membrane / adaptor / IMMUNE SYSTEM | |||||||||||||||||||||
Function / homology | ![]() STING mediated induction of host immune responses / proton channel activity / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / cGAS/STING signaling pathway / reticulophagy / autophagosome membrane / positive regulation of macroautophagy / autophagosome assembly / autophagosome ...STING mediated induction of host immune responses / proton channel activity / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / cGAS/STING signaling pathway / reticulophagy / autophagosome membrane / positive regulation of macroautophagy / autophagosome assembly / autophagosome / positive regulation of type I interferon production / activation of innate immune response / positive regulation of interferon-beta production / endoplasmic reticulum-Golgi intermediate compartment membrane / Neutrophil degranulation / protein complex oligomerization / cytoplasmic vesicle / defense response to virus / Golgi membrane / innate immune response / endoplasmic reticulum membrane / perinuclear region of cytoplasm / protein homodimerization activity / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||||||||||||||
![]() | Shang G / Zhang C | |||||||||||||||||||||
Funding support | ![]()
| |||||||||||||||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 16.8 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 12 KB 12 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 6.1 KB | Display | ![]() |
Images | ![]() | 166.3 KB | ||
Filedesc metadata | ![]() | 5.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 519.7 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 519.3 KB | Display | |
Data in XML | ![]() | 8.7 KB | Display | |
Data in CIF | ![]() | 11.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6nt6MC ![]() 0502C ![]() 0504C ![]() 0505C ![]() 6nt5C ![]() 6nt7C ![]() 6nt8C M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | primary map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.84 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
-Entire : full-length chicken STING
Entire | Name: full-length chicken STING |
---|---|
Components |
|
-Supramolecule #1: full-length chicken STING
Supramolecule | Name: full-length chicken STING / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Stimulator of interferon genes protein
Macromolecule | Name: Stimulator of interferon genes protein / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 44.20707 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPQDPSTRSS PARLLIPEPR AGRARHAACV LLAVCFVVLF LSGEPLAPII RSVCTQLAAL QLGVLLKGCC CLAEEIFHLH SRHHGSLWQ VLCSCFPPRW YLALLLVGGS AYLDPPEDNG HSPRLALTLS CLCQLLVLAL GLQKLSAVEV SELTESSKKN V AHGLAWSY ...String: MPQDPSTRSS PARLLIPEPR AGRARHAACV LLAVCFVVLF LSGEPLAPII RSVCTQLAAL QLGVLLKGCC CLAEEIFHLH SRHHGSLWQ VLCSCFPPRW YLALLLVGGS AYLDPPEDNG HSPRLALTLS CLCQLLVLAL GLQKLSAVEV SELTESSKKN V AHGLAWSY YIGYLKVVLP RLKECMEELS RTNPMLRAHR DTWKLHILVP LGCDIWDDLE KADSNIQYLA DLPETILTRA GI KRRVYKH SLYVIRDKDN KLRPCVLEFA SPLQTLCAMS QDDCAAFSRE QRLEQARLFY RSLRDILGSS KECAGLYRLI AYE EPAEPE SHFLSGLILW HLQQQQREEY MVQEELPLGT SSVELSLQVS SSDLPQPLRS DCPGIHRPDY KDDDDK UniProtKB: Stimulator of interferon genes protein |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 4.5 mg/mL |
---|---|
Buffer | pH: 8 |
Grid | Pretreatment - Type: GLOW DISCHARGE / Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
+
Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
---|---|
Output model | ![]() PDB-6nt6: |