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Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms

Author

Listed:
  • Jiaqi Fu

    (The First Hospital of Jilin University)

  • Siying Li

    (The First Hospital of Jilin University)

  • Hongxin Guan

    (Fujian Normal University)

  • Chuang Li

    (Purdue University)

  • Yan-Bo Zhao

    (Fujian Normal University)

  • Tao-Tao Chen

    (Fujian Normal University)

  • Wei Xian

    (Peking University Health Science Center)

  • Zhengrui Zhang

    (Purdue University)

  • Yao Liu

    (Purdue University)

  • Qingtian Guan

    (The First Hospital of Jilin University)

  • Jingting Wang

    (Fujian Normal University)

  • Qiuhua Lu

    (Fujian Normal University)

  • Lina Kang

    (Fujian Normal University)

  • Si-Ru Zheng

    (Fujian Normal University)

  • Jinyu Li

    (Fuzhou University)

  • Shoujing Cao

    (Fuzhou University)

  • Chittaranjan Das

    (Purdue University)

  • Xiaoyun Liu

    (Peking University Health Science Center)

  • Lei Song

    (The First Hospital of Jilin University)

  • Songying Ouyang

    (Fujian Normal University)

  • Zhao-Qing Luo

    (Purdue University)

Abstract

The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.

Suggested Citation

  • Jiaqi Fu & Siying Li & Hongxin Guan & Chuang Li & Yan-Bo Zhao & Tao-Tao Chen & Wei Xian & Zhengrui Zhang & Yao Liu & Qingtian Guan & Jingting Wang & Qiuhua Lu & Lina Kang & Si-Ru Zheng & Jinyu Li & Sh, 2024. "Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50311-2
    DOI: 10.1038/s41467-024-50311-2
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