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Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system

Nature Structural & Molecular Biology volume 19, pages 722–724 (2012)Cite this article

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Abstract

STING (stimulator of interferon genes) is an innate immune sensor of cyclic dinucleotides that regulates the induction of type I interferons. STING's C-terminal domain forms a V-shaped dimer and binds a cyclic diguanylate monophosphate (c-di-GMP) at the dimer interface by both direct and solvent-mediated hydrogen bonds. Guanines of c-di-GMP stack against the phenolic rings of a conserved tyrosine, and mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling.

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Figure 1: STING forms a dimer and binds c-di-GMP at the dimer interface.
Figure 2: Structural basis of c-di-GMP recognition and the dimer interface of STING.
Figure 3: Mutations at the nucleotide binding surface reduce c-di-GMP binding and affect STING signaling.

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Acknowledgements

The diffraction data of the SeMet crystals were collected at beamline 11.1 at the Stanford Synchrotron Radiation Lightsource (SSRL). The ITC binding studies were conducted in T. Begley's laboratory. This research is supported by the US National Institute of Health (grants AI087741 to P.L. and AI073335 to C.C.K.).

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA

    Chang Shu, Tylan Watts & Pingwei Li

  2. Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA

    Guanghui Yi & C Cheng Kao

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  1. Chang Shu
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  2. Guanghui Yi
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  3. Tylan Watts
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  4. C Cheng Kao
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Contributions

C.S. crystallized the protein and conducted the binding and kinase assays. P.L. determined the structures. G.Y. conducted the IFN-β reporter assays. T.W. helped with the data collection. P.L., C.C.K., C.S. and T.W. wrote the paper.

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Correspondence to Pingwei Li.

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The authors declare no competing financial interests.

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Shu, C., Yi, G., Watts, T. et al. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat Struct Mol Biol 19, 722–724 (2012). https://doi.org/10.1038/nsmb.2331

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