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Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation

Author

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  • Donghyun Ka

    (Seoul National University)

  • Hyejin Oh

    (Seoul National University
    Seoul National University)

  • Eunyoung Park

    (Seoul National University)

  • Jeong-Han Kim

    (Seoul National University
    Seoul National University)

  • Euiyoung Bae

    (Seoul National University
    Seoul National University)

Abstract

The intense arms race between bacteria and phages has led to the development of diverse antiphage defense systems in bacteria. Unlike well-known restriction-modification and CRISPR-Cas systems, recently discovered systems are poorly characterized. One such system is the Thoeris defense system, which consists of two genes, thsA and thsB. Here, we report structural and functional analyses of ThsA and ThsB. ThsA exhibits robust NAD+ cleavage activity and a two-domain architecture containing sirtuin-like and SLOG-like domains. Mutation analysis suggests that NAD+ cleavage is linked to the antiphage function of Thoeris. ThsB exhibits a structural resemblance to TIR domain proteins such as nucleotide hydrolases and Toll-like receptors, but no enzymatic activity is detected in our in vitro assays. These results further our understanding of the molecular mechanism underlying the Thoeris defense system, highlighting a unique strategy for bacterial antiphage resistance via NAD+ degradation.

Suggested Citation

  • Donghyun Ka & Hyejin Oh & Eunyoung Park & Jeong-Han Kim & Euiyoung Bae, 2020. "Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16703-w
    DOI: 10.1038/s41467-020-16703-w
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    Cited by:

    1. Xinmi Song & Sheng Lei & Shunhang Liu & Yanqiu Liu & Pan Fu & Zhifeng Zeng & Ke Yang & Yu Chen & Ming Li & Qunxin She & Wenyuan Han, 2023. "Catalytically inactive long prokaryotic Argonaute systems employ distinct effectors to confer immunity via abortive infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jiafeng Huang & Keli Zhu & Yina Gao & Feng Ye & Zhaolong Li & Yao Ge & Songqing Liu & Jing Yang & Ang Gao, 2024. "Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Ning Cui & Jun-Tao Zhang & Zhuolin Li & Xin-Yang Wei & Jie Wang & Ning Jia, 2024. "Tetramerization-dependent activation of the Sir2-associated short prokaryotic Argonaute immune system," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    4. Ruiwen Wang & Qi Xu & Zhuoxi Wu & Jialu Li & Hao Guo & Tianzhui Liao & Yuan Shi & Ling Yuan & Haishan Gao & Rong Yang & Zhubing Shi & Faxiang Li, 2024. "The structural basis of the activation and inhibition of DSR2 NADase by phage proteins," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Jun-Tao Zhang & Xiao-Yu Liu & Zhuolin Li & Xin-Yang Wei & Xin-Yi Song & Ning Cui & Jirui Zhong & Hongchun Li & Ning Jia, 2024. "Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Shuangshuang Wang & Sirong Kuang & Haiguang Song & Erchao Sun & Mengling Li & Yuepeng Liu & Ziwei Xia & Xueqi Zhang & Xialin Wang & Jiumin Han & Venigalla B. Rao & Tingting Zou & Chen Tan & Pan Tao, 2024. "The role of TIR domain-containing proteins in bacterial defense against phages," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Hang Yin & Xuzichao Li & Xiaoshen Wang & Chendi Zhang & Jiaqi Gao & Guimei Yu & Qiuqiu He & Jie Yang & Xiang Liu & Yong Wei & Zhuang Li & Heng Zhang, 2024. "Insights into the modulation of bacterial NADase activity by phage proteins," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Xiangkai Zhen & Xiaolong Xu & Le Ye & Song Xie & Zhijie Huang & Sheng Yang & Yanhui Wang & Jinyu Li & Feng Long & Songying Ouyang, 2024. "Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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