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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2012 May 15

PMID 22579474

Citations 178

Authors

Songying Ouyang

Xianqiang Song

Yaya Wang

Heng Ru

Neil Shaw

Yan Jiang

Fengfeng Niu

Yanping Zhu

Weicheng Qiu

Kislay Parvatiyar

Yang Li

Rongguang Zhang

Genhong Cheng

Zhi-Jie Liu

Affiliations

Soon will be listed here.

Abstract

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.

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