9DAT

STING oligomer bound to PI(3,5)P2

これはPDB形式変換不可エントリーです。

9DAT の概要

• エントリーDOI: 10.2210/pdb9dat/pdb
• 関連するPDBエントリー: 9DAN
• EMDBエントリー: 46697
• 分子名称: Stimulator of interferon genes protein, 4-({[4-(2-tert-butyl-5,5-dimethyl-1,3-dioxan-2-yl)phenyl]methyl}amino)-3-methoxybenzoic acid, (2R)-3-{[(R)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl di[(9Z)-octadec-9-enoate], ... (5 entities in total)
• 機能のキーワード: sting, lipid, oligomerization, signaling protein, signaling protein-activator complex, signaling protein/activator
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 163437.06

構造登録者

Li, J.,Zhang, X.,Bai, X. (登録日: 2024-08-22, 公開日: 2025-12-17, 最終更新日: 2026-02-18)

主引用文献

Li, J.,Tan, J.X.,Chen, Z.J.,Zhang, X.,Bai, X.C.
Regulation of STING activation by phosphoinositide and cholesterol.
Nature, 2026

PubMed 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 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.

PubMed: 41639452
DOI: 10.1038/s41586-025-10076-0

実験手法

ELECTRON MICROSCOPY (2.9 Å)