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- EMDB-46694: STING oligomer bound to PI(4,5)P2 -

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Basic information

Entry
Database: EMDB / ID: EMD-46694
TitleSTING oligomer bound to PI(4,5)P2
Map data
Sample
  • Complex: STING oligomer bound to its ligand cGAMP, a synthetic activator named STG2, Cholesteryl hemisuccinate and PI(4,5)P2
    • Protein or peptide: Stimulator of interferon genes protein
  • Ligand: 4-({[4-(2-tert-butyl-5,5-dimethyl-1,3-dioxan-2-yl)phenyl]methyl}amino)-3-methoxybenzoic acid
  • Ligand: (2R)-3-{[(S)-hydroxy{[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl di[(9Z)-octadec-9-enoate]
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: cGAMP
KeywordsSTING / lipid / oligomerization / SIGNALING PROTEIN / SIGNALING PROTEIN-ACTIVATOR complex
Function / homology
Function and homology information


STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / cGAS/STING signaling pathway ...STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / cGAS/STING signaling pathway / proton channel activity / reticulophagy / pattern recognition receptor signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / protein complex oligomerization / autophagosome membrane / positive regulation of macroautophagy / autophagosome assembly / positive regulation of type I interferon production / : / cellular response to interferon-beta / positive regulation of defense response to virus by host / signaling adaptor activity / endoplasmic reticulum-Golgi intermediate compartment membrane / antiviral innate immune response / activation of innate immune response / protein serine/threonine kinase binding / positive regulation of interferon-beta production / autophagosome / Regulation of innate immune responses to cytosolic DNA / secretory granule membrane / cytoplasmic vesicle membrane / SARS-CoV-1 activates/modulates innate immune responses / peroxisome / regulation of inflammatory response / defense response to virus / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / endosome / cilium / ciliary basal body / Golgi membrane / innate immune response / ubiquitin protein ligase binding / Neutrophil degranulation / protein kinase binding / endoplasmic reticulum membrane / 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
: / STING transmembrane domain / : / : / Stimulator of interferon genes protein / Stimulator of interferon genes protein, C-terminal domain superfamily / STING ligand-binding domain
Similarity search - Domain/homology
Stimulator of interferon genes protein
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.6 Å
AuthorsLi J / Zhang X / Bai X
Funding support United States, 3 items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA273595 United States
Welch FoundationI-1702 United States
Welch FoundationI-1944 United States
CitationJournal: To Be Published
Title: Structural basis for the roles of phosphoinositide phosphates and cholesterol in STING activation
Authors: Jie L / Zhang X / Bai X
History
DepositionAug 22, 2024-
Header (metadata) releaseDec 17, 2025-
Map releaseDec 17, 2025-
UpdateDec 17, 2025-
Current statusDec 17, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46694.png

Downloads & links

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Map

FileDownload / File: emd_46694.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 300 pix.
= 324. Å		1.08 Å/pix.
x 300 pix.
= 324. Å		1.08 Å/pix.
x 300 pix.
= 324. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.08 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.006
Minimum - Maximum-0.023406541 - 0.068456315
Average (Standard dev.)0.000095350304 (±0.0014117998)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 324.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_46694_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_46694_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : STING oligomer bound to its ligand cGAMP, a synthetic activator n...

EntireName: STING oligomer bound to its ligand cGAMP, a synthetic activator named STG2, Cholesteryl hemisuccinate and PI(4,5)P2
Components
  • Complex: STING oligomer bound to its ligand cGAMP, a synthetic activator named STG2, Cholesteryl hemisuccinate and PI(4,5)P2
    • Protein or peptide: Stimulator of interferon genes protein
  • Ligand: 4-({[4-(2-tert-butyl-5,5-dimethyl-1,3-dioxan-2-yl)phenyl]methyl}amino)-3-methoxybenzoic acid
  • Ligand: (2R)-3-{[(S)-hydroxy{[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl di[(9Z)-octadec-9-enoate]
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: cGAMP

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Supramolecule #1: STING oligomer bound to its ligand cGAMP, a synthetic activator n...

SupramoleculeName: STING oligomer bound to its ligand cGAMP, a synthetic activator named STG2, Cholesteryl hemisuccinate and PI(4,5)P2
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Stimulator of interferon genes protein

MacromoleculeName: Stimulator of interferon genes protein / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.553398 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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 EKEEVTVGTS SGLEVLFQ

UniProtKB: Stimulator of interferon genes protein

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Macromolecule #2: 4-({[4-(2-tert-butyl-5,5-dimethyl-1,3-dioxan-2-yl)phenyl]methyl}a...

MacromoleculeName: 4-({[4-(2-tert-butyl-5,5-dimethyl-1,3-dioxan-2-yl)phenyl]methyl}amino)-3-methoxybenzoic acid
type: ligand / ID: 2 / Number of copies: 2 / Formula: Y6H
Molecular weightTheoretical: 427.533 Da
Chemical component information

ChemComp-Y6H:
4-({[4-(2-tert-butyl-5,5-dimethyl-1,3-dioxan-2-yl)phenyl]methyl}amino)-3-methoxybenzoic acid

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Macromolecule #3: (2R)-3-{[(S)-hydroxy{[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-bi...

MacromoleculeName: (2R)-3-{[(S)-hydroxy{[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl di[(9Z)-octadec-9-enoate]
type: ligand / ID: 3 / Number of copies: 2 / Formula: A1BBG
Molecular weightTheoretical: 1.023066 KDa

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Macromolecule #4: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

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Macromolecule #5: cGAMP

MacromoleculeName: cGAMP / type: ligand / ID: 5 / Number of copies: 2 / Formula: 1SY
Molecular weightTheoretical: 674.411 Da
Chemical component information

ChemComp-1SY:
cGAMP

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.2 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: EMDB MAP
EMDB ID:

29282

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 242771
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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