6CFF

Stimulator of Interferon Genes Human

6CFF の概要

• エントリーDOI: 10.2210/pdb6cff/pdb
• 分子名称: Stimulator of interferon genes protein, (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ]tetraoxadiphosphacyclododecine-3,5,10,12-tetrol 5,12-dioxide (3 entities in total)
• 機能のキーワード: human sting, complex, cyclic-di-amp, tmem173, wild type, 230g/232r, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27782.01

構造登録者

Fernandez, D.,Li, L.,Ergun, S.L. (登録日: 2018-02-14, 公開日: 2019-03-13, 最終更新日: 2024-03-13)

主引用文献

Ergun, S.L.,Fernandez, D.,Weiss, T.M.,Li, L.
STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition.
Cell, 178:290-301.e10, 2019

PubMed Abstract: How the central innate immune protein, STING, is activated by its ligands remains unknown. Here, using structural biology and biochemistry, we report that the metazoan second messenger 2'3'-cGAMP induces closing of the human STING homodimer and release of the STING C-terminal tail, which exposes a polymerization interface on the STING dimer and leads to the formation of disulfide-linked polymers via cysteine residue 148. Disease-causing hyperactive STING mutations either flank C148 and depend on disulfide formation or reside in the C-terminal tail binding site and cause constitutive C-terminal tail release and polymerization. Finally, bacterial cyclic-di-GMP induces an alternative active STING conformation, activates STING in a cooperative manner, and acts as a partial antagonist of 2'3'-cGAMP signaling. Our insights explain the tight control of STING signaling given varying background activation signals and provide a therapeutic hypothesis for autoimmune syndrome treatment.

PubMed: 31230712
DOI: 10.1016/j.cell.2019.05.036

実験手法

X-RAY DIFFRACTION (2.396 Å)