Structural Analysis of the STING Adaptor Protein Reveals a Hydrophobic Dimer Interface and Mode of Cyclic di-GMP Binding

被引：319

作者：

Ouyang, Songying ^{[2
]}

Song, Xianqiang ^{[2
]}

Wang, Yaya ^{[1
]}

Ru, Heng ^{[2
]}

Shaw, Neil ^{[2
]}

Jiang, Yan ^{[2
]}

Niu, Fengfeng ^{[2
]}

Zhu, Yanping ^{[2
]}

Qiu, Weicheng ^{[2
]}

Parvatiyar, Kislay ^{[1
]}

Li, Yang ^{[2
]}

Zhang, Rongguang ^{[2
]}

Cheng, Genhong ^{[1
]}

Liu, Zhi-Jie ^{[2
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[2] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China

来源：

IMMUNITY | 2012年 / 36卷 / 06期

基金：

中国国家自然科学基金;

关键词：

ALLOSTERIC CONTROL; MACROMOLECULAR STRUCTURES; SEQUENCE; SERVER; MPYS; IDENTIFICATION; CONSERVATION; DIFFRACTION; REFINEMENT; ACTIVATION;

D O I：

10.1016/j.immuni.2012.03.019

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

STING is an essential signaling molecule for DNA and cyclic di-GMP (c-di-GMP)-mediated type I interferon (IFN) production via TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway. It contains an N-terminal transmembrane region and a cytosolic C-terminal domain (CTD). Here, we describe crystal structures of STING CTD alone and complexed with c-di-GMP in a unique binding mode. The strictly conserved aa 153-173 region was shown to be cytosolic and participated in dimerization via hydrophobic interactions. The STING CTD functions as a dimer and the dimerization was independent of posttranslational modifications. Binding of c-di-GMP enhanced interaction of a shorter construct of STING CTD (residues 139-344) with TBK1. This suggests an extra TBK1 binding site, other than serine 358. This study provides a glimpse into the unique architecture of STING and sheds light on the mechanism of c-di-GMP-mediated TBK1 signaling.

引用

页码：1073 / 1086

页数：14

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