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Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP

Nature Structural & Molecular Biology volume 19, pages 725–727 (2012)Cite this article

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Abstract

STING functions as both an adaptor protein signaling cytoplasmic double-stranded DNA and a direct immunosensor of cyclic diguanylate monophosphate (c-di-GMP). The crystal structures of the C-terminal domain of human STING (STINGCTD) and its complex with c-di-GMP reveal how STING recognizes c-di-GMP. In response to c-di-GMP binding, two surface loops, which serve as a gate and latch of the cleft formed by the dimeric STINGCTD, undergo rearrangements to interact with the ligand.

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Figure 1: Structure of human STINGCTD in complex with c-di-GMP.
Figure 2: c-di-GMP recognition by STINGCTD.
Figure 3: Conformational changes in STINGCTD upon c-di-GMP binding.

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Acknowledgements

We thank R. Qiu for providing human cDNA library, the staff at Shanghai Synchrotron Radiation Facility beamline 17U for assistance with data collection. This work was supported by the State Key Laboratory of Microbial Technology, Shandong University, by Hi-Tech Research and Development Program of China grant no. 2006AA02A324 to L.G. and by National Nature Science Foundation of China grant no. 31000330 to D.Z.

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  1. Guijun Shang, Deyu Zhu, Ning Li and Junbing Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, Jinan, China

    Guijun Shang, Deyu Zhu, Ning Li, Junbing Zhang, Chunyuan Zhu, Defen Lu, Cuilan Liu, Qian Yu, Yanyu Zhao, Sujuan Xu & Lichuan Gu

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  1. Guijun Shang
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Contributions

G.S., D.Z., N.L., J.Z. and L.G. designed the research; G.S., D.Z., N.L., J.Z., C.Z., D.L., C.L., Q.Y. and Y.Z. performed the experiments; G.S., D.Z., N.L., J.Z., S.X. and L.G. analyzed data and wrote the paper; all authors contributed to the editing of the manuscript.

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Correspondence to Lichuan Gu.

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Shang, G., Zhu, D., Li, N. et al. Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP. Nat Struct Mol Biol 19, 725–727 (2012). https://doi.org/10.1038/nsmb.2332

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