Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING

Qian Yin, Yuan Tian, Venkataraman Kabaleeswaran, Xiaomo Jiang, Daqi Tu, Michael J. Eck, Zhijian J. Chen, Hao Wu

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133 Scopus citations

Abstract

Detection of foreign materials is the first step of successful immune responses. Stimulator of interferon genes (STING) was shown to directly bind cyclic diguanylate monophosphate (c-di-GMP), a bacterial second messenger, and to elicit strong interferon responses. Here we elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP. The CBD exhibits an α + β fold and is a dimer in the crystal and in solution. Surprisingly, one c-di-GMP molecule binds to the central crevice of a STING dimer, using a series of stacking and hydrogen bonding interactions. We show that STING is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT. The structures provide a remarkable example of pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system.

Original languageEnglish (US)
Pages (from-to)735-745
Number of pages11
JournalMolecular Cell
Volume46
Issue number6
DOIs
Publication statusPublished - Jun 29 2012

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yin, Q., Tian, Y., Kabaleeswaran, V., Jiang, X., Tu, D., Eck, M. J., ... Wu, H. (2012). Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING. Molecular Cell, 46(6), 735-745. https://doi.org/10.1016/j.molcel.2012.05.029