STING 衔接蛋白的结构分析揭示了疏水二聚体界面和环二鸟苷酸结合模式。
Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding.
机构信息
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
出版信息
Immunity. 2012 Jun 29;36(6):1073-86. doi: 10.1016/j.immuni.2012.03.019. Epub 2012 May 10.
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.
摘要
STING 是一种重要的信号分子，可通过 TANK 结合激酶 1（TBK1）和干扰素调节因子 3（IRF3）途径介导 DNA 和环二鸟苷酸（c-di-GMP）介导的 I 型干扰素（IFN）的产生。它包含一个 N 端跨膜区域和一个胞质 C 端结构域（CTD）。在这里，我们描述了 STING CTD 单独的晶体结构和以独特的结合模式与 c-di-GMP 形成的复合物结构。严格保守的 aa 153-173 区域被证明位于胞质中，并通过疏水相互作用参与二聚化。STING CTD 作为二聚体发挥作用，其二聚化不依赖于翻译后修饰。c-di-GMP 的结合增强了 STING CTD 较短结构域（残基 139-344）与 TBK1 的相互作用。这表明存在除丝氨酸 358 以外的额外 TBK1 结合位点。本研究提供了对 STING 独特结构的初步了解，并阐明了 c-di-GMP 介导的 TBK1 信号转导的机制。
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