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The structural basis for the sensing and binding of cyclic di-GMP by STING

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Abstract

STING (stimulator of interferon genes) is an essential signaling adaptor that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP). STING's structure and its binding mechanism to cyclic dinucleotides were unknown. We report here the crystal structures of the STING cytoplasmic domain and its complex with c-di-GMP, thus providing the structural basis for understanding STING function.

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Figure 1: Overall structure of hSTING in complex with c-di-GMP and multiple sequence alignment of STING from different species.
Figure 2: Ribbon representation of hSTING structures.

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Acknowledgements

We thank the Shanghai Synchrotron Radiation Facilities (SSRF), China, and the Photon Factory (PF) at High Energy Accelerator Research Organization (KEK), Japan for help with data collection, and M. Tian and L. Finci for language editing. This work was supported by funds from the National Basic Research Program of China 973 (No. 2011CB911103 to X.-D.S.) and National High Technology, 863 Program (2006AA02A317 to X.-D.S.). Peking University's 985 and 211 grants are highly appreciated.

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Author notes

  1. Yi-He Huang and Xiang-Yu Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China

    Yi-He Huang, Xiang-Yu Liu, Xiao-Xia Du, Zheng-Fan Jiang & Xiao-Dong Su

  2. Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China

    Yi-He Huang, Xiang-Yu Liu, Xiao-Xia Du & Xiao-Dong Su

  3. Peking University Shenzhen Graduate School, Shenzhen, China

    Yi-He Huang & Xiao-Xia Du

Authors
  1. Yi-He Huang
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  2. Xiang-Yu Liu
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  3. Xiao-Xia Du
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  4. Zheng-Fan Jiang
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  5. Xiao-Dong Su
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Contributions

Y.-H.H., assisted by X.-X.D., accomplished protein expression, purification and other biochemistry experiments as well as crystallization, performed some data analysis and prepared the manuscript. Data collection and processing were performed by Y.-H.H., X.-Y.L. and X.-D.S. Phase determination, model building and structure refinement were accomplished by X.-Y.L., Y.-H.H. and X.-D.S. Y.-H.H., X.-Y.L. and X.-D.S. analyzed the structures and wrote the paper. Z.-F.J. and X.-D.S. initiated, designed and supervised the project.

Corresponding author

Correspondence to Xiao-Dong Su.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5 and Supplementary Table 1 (PDF 748 kb)

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Huang, YH., Liu, XY., Du, XX. et al. The structural basis for the sensing and binding of cyclic di-GMP by STING. Nat Struct Mol Biol 19, 728–730 (2012). https://doi.org/10.1038/nsmb.2333

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