Nature Communications (Jul 2024)
Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms
- 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,
- Shoujing Cao,
- Chittaranjan Das,
- Xiaoyun Liu,
- Lei Song,
- Songying Ouyang,
- Zhao-Qing Luo
Affiliations
- Jiaqi Fu
- Department of Respiratory Medicine, Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University
- Siying Li
- Department of Respiratory Medicine, Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University
- Hongxin Guan
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Chuang Li
- Department of Biological Sciences, Purdue University
- Yan-Bo Zhao
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Tao-Tao Chen
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Wei Xian
- Department of Microbiology, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center
- Zhengrui Zhang
- Department of Chemistry, Purdue University
- Yao Liu
- Department of Biological Sciences, Purdue University
- Qingtian Guan
- Department of Respiratory Medicine, Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University
- Jingting Wang
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Qiuhua Lu
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Lina Kang
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Si-Ru Zheng
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Jinyu Li
- College of Chemistry, Fuzhou University
- Shoujing Cao
- College of Chemistry, Fuzhou University
- Chittaranjan Das
- Department of Chemistry, Purdue University
- Xiaoyun Liu
- Department of Microbiology, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center
- Lei Song
- Department of Respiratory Medicine, Center for Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University
- Songying Ouyang
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University
- Zhao-Qing Luo
- Department of Biological Sciences, Purdue University
- DOI
- https://doi.org/10.1038/s41467-024-50311-2
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 13
Abstract
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.
