8IK3

Structure of Stimulator of interferon genes/ligand complex

8IK3 の概要

• エントリーDOI: 10.2210/pdb8ik3/pdb
• 関連するPDBエントリー: 8IK0
• EMDBエントリー: 35504
• 分子名称: Stimulator of interferon genes protein,Immune protein Tsi3, cGAMP (2 entities in total)
• 機能のキーワード: complex, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 467921.61

構造登録者

Lu, D.F.,Shang, G.J. (登録日: 2023-02-28, 公開日: 2023-05-17, 最終更新日: 2025-07-23)

主引用文献

Liu, S.,Yang, B.,Hou, Y.,Cui, K.,Yang, X.,Li, X.,Chen, L.,Liu, S.,Zhang, Z.,Jia, Y.,Xie, Y.,Xue, Y.,Li, X.,Yan, B.,Wu, C.,Deng, W.,Qi, J.,Lu, D.,Gao, G.F.,Wang, P.,Shang, G.
The mechanism of STING autoinhibition and activation.
Mol.Cell, 83:1502-1518.e10, 2023

PubMed Abstract: 2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway.

PubMed: 37086726
DOI: 10.1016/j.molcel.2023.03.029

実験手法

ELECTRON MICROSCOPY (3.3 Å)