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Structural basis for broad anti-phage immunity by DISARM

Author

Listed:
  • Jack P. K. Bravo

    (University of Texas at Austin)

  • Cristian Aparicio-Maldonado

    (Delft University of Technology
    Kavli Institute of Nanoscience
    University of Southampton)

  • Franklin L. Nobrega

    (University of Southampton)

  • Stan J. J. Brouns

    (Delft University of Technology
    Kavli Institute of Nanoscience)

  • David W. Taylor

    (University of Texas at Austin
    University of Texas at Austin
    University of Texas at Austin
    Dell Medical School)

Abstract

In the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an unmethylated phage DNA mimetic. These structures reveal that DrmAB core complex is autoinhibited by a trigger loop (TL) within DrmA and binding to DNA substrates containing a 5′ overhang dislodges the TL, initiating a long-range structural rearrangement for DrmAB activation. Together with structure-guided in vivo studies, our work provides insights into the mechanism of phage DNA recognition and specific activation of this widespread antiviral defense system.

Suggested Citation

  • Jack P. K. Bravo & Cristian Aparicio-Maldonado & Franklin L. Nobrega & Stan J. J. Brouns & David W. Taylor, 2022. "Structural basis for broad anti-phage immunity by DISARM," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30673-1
    DOI: 10.1038/s41467-022-30673-1
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    References listed on IDEAS

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    1. Hannah G. Hampton & Bridget N. J. Watson & Peter C. Fineran, 2020. "The arms race between bacteria and their phage foes," Nature, Nature, vol. 577(7790), pages 327-336, January.
    2. Jun Yu & Pierre Raia & Chloe M. Ghent & Tobias Raisch & Yashar Sadian & Simone Cavadini & Pramod M. Sabale & David Barford & Stefan Raunser & David O. Morgan & Andreas Boland, 2021. "Structural basis of human separase regulation by securin and CDK1–cyclin B1," Nature, Nature, vol. 596(7870), pages 138-142, August.
    3. Asaf Levy & Moran G. Goren & Ido Yosef & Oren Auster & Miriam Manor & Gil Amitai & Rotem Edgar & Udi Qimron & Rotem Sorek, 2015. "CRISPR adaptation biases explain preference for acquisition of foreign DNA," Nature, Nature, vol. 520(7548), pages 505-510, April.
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    1. Xiangkai Zhen & Biao Zhou & Zihe Liu & Xurong Wang & Heyu Zhao & Shuxian Wu & Zekai Li & Jiamin liang & Wanyue Zhang & Qingjian Zhu & Jun He & Xiaoli Xiong & Songying Ouyang, 2024. "Mechanistic basis for the allosteric activation of NADase activity in the Sir2-HerA antiphage defense system," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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