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

Research output: Contribution to journalArticle

122 Citations (Scopus)

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
StatePublished - Jun 29 2012

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Interferons
Genes
Proteins
Host-Pathogen Interactions
Second Messenger Systems
Hydrogen Bonding
bis(3',5')-cyclic diguanylic acid
Immune System

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

Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING. / Yin, Qian; Tian, Yuan; Kabaleeswaran, Venkataraman; Jiang, Xiaomo; Tu, Daqi; Eck, Michael J.; Chen, Zhijian J.; Wu, Hao.

In: Molecular Cell, Vol. 46, No. 6, 29.06.2012, p. 735-745.

Research output: Contribution to journalArticle

Yin, Q, Tian, Y, Kabaleeswaran, V, Jiang, X, Tu, D, Eck, MJ, Chen, ZJ & Wu, H 2012, 'Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING', Molecular Cell, vol. 46, no. 6, pp. 735-745. https://doi.org/10.1016/j.molcel.2012.05.029
Yin Q, Tian Y, Kabaleeswaran V, Jiang X, Tu D, Eck MJ et al. Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING. Molecular Cell. 2012 Jun 29;46(6):735-745. https://doi.org/10.1016/j.molcel.2012.05.029
Yin, Qian ; Tian, Yuan ; Kabaleeswaran, Venkataraman ; Jiang, Xiaomo ; Tu, Daqi ; Eck, Michael J. ; Chen, Zhijian J. ; Wu, Hao. / Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING. In: Molecular Cell. 2012 ; Vol. 46, No. 6. pp. 735-745.
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