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A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1

Author

Listed:
  • Yanan Zhao

    (Harbin Institute of Technology)

  • Jiaojiao Hu

    (Chinese Academy of Sciences)

  • Shan-Shan Yang

    (School of Environment, Harbin Institute of Technology)

  • Jing Zhong

    (Harbin Institute of Technology)

  • Jianping Liu

    (Chinese Academy of Sciences)

  • Shuo Wang

    (Harbin Institute of Technology)

  • Yuzhuo Jiao

    (Harbin Institute of Technology)

  • Fang Jiang

    (Harbin Institute of Technology)

  • Ruiyang Zhai

    (Harbin Institute of Technology)

  • Bingnan Ren

    (Harbin Institute of Technology)

  • Hua Cong

    (Harbin Institute of Technology)

  • Yuwei Zhu

    (Harbin Institute of Technology)

  • Fengtong Han

    (Harbin Institute of Technology)

  • Jixian Zhang

    (Harbin Institute of Technology)

  • Yue Xu

    (Harbin Institute of Technology)

  • Zhiwei Huang

    (Harbin Institute of Technology)

  • Shengnan Zhang

    (Chinese Academy of Sciences)

  • Fan Yang

    (Harbin Institute of Technology)

Abstract

Anti-CRISPRs (Acrs) are natural inhibitors of bacteria’s CRISPR-Cas systems, and have been developed as a safeguard to reduce the off-target effects of CRISPR gene-editing technology. Acrs can directly bind to CRISPR-Cas complexes and inhibit their activities. However, whether this process is under regulation in diverse eukaryotic cellular environments is poorly understood. In this work, we report the discovery of a redox switch for NmeAcrIIC1, which regulates NmeAcrIIC1’s monomer-dimer interconversion and inhibitory activity on Cas9. Further structural studies reveal that a pair of conserved cysteines mediates the formation of inactive NmeAcrIIC1 dimer and directs the redox cycle. The redox switch also applies to the other two AcrIIC1 orthologs. Moreover, by replacing the redox-sensitive cysteines, we generated a robust AcrIIC1 variant that maintains potent inhibitory activity under various redox conditions. Our results reveal a redox-dependent regulation mechanism of Acr, and shed light on the design of superior Acr for CRISPR-Cas systems.

Suggested Citation

  • Yanan Zhao & Jiaojiao Hu & Shan-Shan Yang & Jing Zhong & Jianping Liu & Shuo Wang & Yuzhuo Jiao & Fang Jiang & Ruiyang Zhai & Bingnan Ren & Hua Cong & Yuwei Zhu & Fengtong Han & Jixian Zhang & Yue Xu , 2022. "A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34551-8
    DOI: 10.1038/s41467-022-34551-8
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