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Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion

Author

Listed:
  • Jiafeng Huang

    (Beijing Institute of Technology
    Chinese Academy of Sciences)

  • Keli Zhu

    (Beijing Institute of Technology)

  • Yina Gao

    (Chinese Academy of Sciences)

  • Feng Ye

    (Beijing Institute of Technology)

  • Zhaolong Li

    (Chinese Academy of Sciences)

  • Yao Ge

    (Beijing Institute of Technology)

  • Songqing Liu

    (Chinese Academy of Sciences)

  • Jing Yang

    (Peking University Aerospace School of Clinical Medicine)

  • Ang Gao

    (Beijing Institute of Technology
    Shandong First Medical University & Shandong Academy of Medical Sciences)

Abstract

Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD+, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48291-4
    DOI: 10.1038/s41467-024-48291-4
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    1. 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.

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