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A toxin-deformation dependent inhibition mechanism in the T7SS toxin-antitoxin system of Gram-positive bacteria

Author

Listed:
  • Yongjin Wang

    (Jinan University)

  • Yang Zhou

    (Jinan University)

  • Chaowei Shi

    (University of Science and Technology of China)

  • Jiacong Liu

    (Jinan University)

  • Guohua Lv

    (Jinan University)

  • Huisi Huang

    (Jinan University)

  • Shengrong Li

    (Jinan University)

  • Liping Duan

    (Jinan University)

  • Xinyi Zheng

    (Jinan University)

  • Yue Liu

    (Jinan University)

  • Haibo Zhou

    (Jinan University)

  • Yonghua Wang

    (South China University of Technology)

  • Zhengqiu Li

    (Jinan University)

  • Ke Ding

    (Jinan University)

  • Pinghua Sun

    (Jinan University)

  • Yun Huang

    (Weill Cornell Medicine)

  • Xiaoyun Lu

    (Jinan University)

  • Zhi-Min Zhang

    (Jinan University
    Guangdong Youmei Institute of Intelligent Bio-manufacturing)

Abstract

Toxin EsaD secreted by some S. aureus strains through the type VII secretion system (T7SS) specifically kills those strains lacking the antitoxin EsaG. Here we report the structures of EsaG, the nuclease domain of EsaD and their complex, which together reveal an inhibition mechanism that relies on significant conformational change of the toxin. To inhibit EsaD, EsaG breaks the nuclease domain of EsaD protein into two independent fragments that, in turn, sandwich EsaG. The originally well-folded ββα-metal finger connecting the two fragments is stretched to become a disordered loop, leading to disruption of the catalytic site of EsaD and loss of nuclease activity. This mechanism is distinct from that of the other Type II toxin-antitoxin systems, which utilize an intrinsically disordered region on the antitoxins to cover the active site of the toxins. This study paves the way for developing therapeutic approaches targeting this antagonism.

Suggested Citation

  • Yongjin Wang & Yang Zhou & Chaowei Shi & Jiacong Liu & Guohua Lv & Huisi Huang & Shengrong Li & Liping Duan & Xinyi Zheng & Yue Liu & Haibo Zhou & Yonghua Wang & Zhengqiu Li & Ke Ding & Pinghua Sun & , 2022. "A toxin-deformation dependent inhibition mechanism in the T7SS toxin-antitoxin system of Gram-positive bacteria," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34034-w
    DOI: 10.1038/s41467-022-34034-w
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    References listed on IDEAS

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