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Tetramerization-dependent activation of the Sir2-associated short prokaryotic Argonaute immune system

Author

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  • Ning Cui

    (Southern University of Science and Technology)

  • Jun-Tao Zhang

    (Southern University of Science and Technology)

  • Zhuolin Li

    (Southern University of Science and Technology)

  • Xin-Yang Wei

    (Southern University of Science and Technology)

  • Jie Wang

    (Southern University of Science and Technology)

  • Ning Jia

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

Abstract

Eukaryotic Argonaute proteins (eAgos) utilize short nucleic acid guides to target complementary sequences for RNA silencing, while prokaryotic Agos (pAgos) provide immunity against invading plasmids or bacteriophages. The Sir2-domain associated short pAgo (SPARSA) immune system defends against invaders by depleting NAD+ and triggering cell death. However, the molecular mechanism underlying SPARSA activation remains unknown. Here, we present cryo-EM structures of inactive monomeric, active tetrameric and active NAD+-bound tetrameric SPARSA complexes, elucidating mechanisms underlying SPARSA assembly, guide RNA preference, target ssDNA-triggered SPARSA tetramerization, and tetrameric-dependent NADase activation. Short pAgos form heterodimers with Sir2-APAZ, favoring short guide RNA with a 5′-AU from ColE-like plasmids. RNA-guided recognition of the target ssDNA triggers SPARSA tetramerization via pAgo- and Sir2-mediated interactions. The resulting tetrameric Sir2 rearrangement aligns catalytic residue H186 for NAD+ hydrolysis. These insights advance our understanding of Sir2-domain associated pAgos immune systems and should facilitate the development of a short pAgo-associated biotechnological toolbox.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52910-5
    DOI: 10.1038/s41467-024-52910-5
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    References listed on IDEAS

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    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. Zhangfei Shen & Xiao-Yuan Yang & Shiyu Xia & Wei Huang & Derek J. Taylor & Kotaro Nakanishi & Tian-Min Fu, 2023. "Oligomerization-mediated activation of a short prokaryotic Argonaute," Nature, Nature, vol. 621(7977), pages 154-161, September.
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