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Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling.

Ting WangXiaonan SongJiaxing TanWei XianXingtong ZhouMingru YuXiaofei WangYan XuTing WuKeke YuanYu RanBing YangGaofeng FanXiaoyun LiuYan ZhouYongqun Zhu
Published in: Nature (2024)
AMPylation is a posttranslational modification that generally modifies amino acid side chains of proteins with adenosine monophosphate (AMP) 1,2 . Here we report that with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity toward the phosphoryl group of phosphoribose on PR R42 -Ub that is generated by the SidE family effectors and deubiquitinases DupA/B in an E1/E2-independent ubiquitination process 3-7 . The product of LnaB is further hydrolyzed by an ADP-ribosyl hydrolase, MavL, to be Ub, thereby preventing accumulation of PR R42 -Ub and ADPR R42 -Ub and protecting the canonical ubiquitination in host cells. LnaB represents a large family of AMPylases adopting a common structural fold, which is distinct from those of the previously known AMPylases, in bacterial pathogens of more than 20 species. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity toward phosphorylated residues and produces unique ADPylation modification in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family kinases 8,9 , which dampens the host downstream phosphorylation signaling. Structural studies revealed the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study presents an unprecedented regulation and molecular mechanism in bacterial pathogenesis and protein phosphorylation.
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