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- EMDB-71619: STING oligomer bound to PI(3,5)P2 without C53 or STG2 -

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Basic information

Entry
Database: EMDB / ID: EMD-71619
TitleSTING oligomer bound to PI(3,5)P2 without C53 or STG2
Map data
Sample
  • Complex: STING oligomer bound to its ligand cGAMP, Cholesteryl hemisuccinate and PI(3,5)P2
KeywordsSTING / lipid / oligomerization / SIGNALING PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.1 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: Nature / Year: 2026
Title: Regulation of STING activation by phosphoinositide and cholesterol.
Authors: Jie Li / Jay Xiaojun Tan / Zhijian J Chen / Xuewu Zhang / Xiao-Chen Bai /
Abstract: Stimulator of interferon genes (STING) is an essential adaptor in the cytosolic DNA-sensing innate immune pathway. STING is activated by cyclic GMP-AMP (cGAMP) produced by the DNA sensor cGAMP ...Stimulator of interferon genes (STING) is an essential adaptor in the cytosolic DNA-sensing innate immune pathway. STING is activated by cyclic GMP-AMP (cGAMP) produced by the DNA sensor cGAMP synthase (cGAS). cGAMP-induced high-order oligomerization and translocation of STING from the endoplasmic reticulum to the Golgi and post-Golgi vesicles are critical for STING activation. Other studies have shown that phosphatidylinositol phosphates (PtdInsPs) and cholesterol also have important roles in STING activation, but the underlying mechanisms remain unclear. Here we demonstrate that cGAMP-induced high-order oligomerization of STING is enhanced strongly by phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P and PtdIns(4,5)P, and by PtdIns4P to a lesser extent. Our cryo-electron microscopy structures reveal that PtdInsPs together with cholesterol bind at the interface between STING dimers, directly promoting the high-order oligomerization. The structures also provide an explanation for the preference of the STING oligomer to different PtdInsPs. Mutational and biochemical analyses confirm the binding modes of PtdInsPs and cholesterol and their roles in STING activation. Our findings shed light on the regulatory mechanisms of STING mediated by specific lipids, which may underlie the role of intracellular trafficking in dictating STING signalling.
History
DepositionJul 7, 2025-
Header (metadata) releaseDec 17, 2025-
Map releaseDec 17, 2025-
UpdateJul 1, 2026-
Current statusJul 1, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71619.png

Downloads & links

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Map

FileDownload / File: emd_71619.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 240 pix.
= 198.24 Å		0.83 Å/pix.
x 240 pix.
= 198.24 Å		0.83 Å/pix.
x 240 pix.
= 198.24 Å

Surface

Projections

Slices (1/3)

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.826 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0017
Minimum - Maximum-0.007047229 - 0.0122719025
Average (Standard dev.)0.00003777206 (±0.0004393147)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 198.23999 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_71619_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_71619_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Sample components

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Entire : STING oligomer bound to its ligand cGAMP, Cholesteryl hemisuccina...

EntireName: STING oligomer bound to its ligand cGAMP, Cholesteryl hemisuccinate and PI(3,5)P2
Components
  • Complex: STING oligomer bound to its ligand cGAMP, Cholesteryl hemisuccinate and PI(3,5)P2

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Supramolecule #1: STING oligomer bound to its ligand cGAMP, Cholesteryl hemisuccina...

SupramoleculeName: STING oligomer bound to its ligand cGAMP, Cholesteryl hemisuccinate and PI(3,5)P2
type: complex / ID: 1 / Parent: 0
Source (natural)Organism: Homo sapiens (human)

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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

MicroscopeTFS 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 reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 39819
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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