Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling

Autor: Wang T; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China., Song X; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China., Tan J; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Shanghai Institute for Advanced Study, Zhejiang University, Shanghai, China., Xian W; Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China., Zhou X; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China., Yu M; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China., Wang X; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China., Xu Y; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China., Wu T; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China., Yuan K; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China., Ran Y; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China., Yang B; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China., Fan G; School of Life Science and Technology, ShanghaiTech University, Shanghai, China., Liu X; Department of Microbiology and Infectious Disease Center, NHC Key Laboratory of Medical Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. xiaoyun.liu@bjmu.edu.cn., Zhou Y; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China. zhouyanlsi@zju.edu.cn.; Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China. zhouyanlsi@zju.edu.cn., Zhu Y; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine and College of Animal Sciences, Life Sciences Institute, Zhejiang University, Hangzhou, China. zhuyongqun@zju.edu.cn.; MOE Key Laboratory of Biosystems Homeostasis and Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China. zhuyongqun@zju.edu.cn.; Shanghai Institute for Advanced Study, Zhejiang University, Shanghai, China. zhuyongqun@zju.edu.cn.; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China. zhuyongqun@zju.edu.cn.; MOA Key Laboratory of Animal Virology, Center for Veterinary Sciences, Zhejiang University, Hangzhou, China. zhuyongqun@zju.edu.cn.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Jul; Vol. 631 (8020), pp. 393-401. Date of Electronic Publication: 2024 May 22.
DOI: 10.1038/s41586-024-07573-z
Abstrakt: AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins 1,2 . Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PR R42 -Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process 3-7 . The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PR R42 -Ub and ADPR R42 -Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases 8,9 , which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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