%0 Journal Article
%T Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms.
%A Fu J
%A Li S
%A Guan H
%A Li C
%A Chen TT
%A Xian W
%A Zhang Z
%A Liu Y
%A Guan Q
%A Wang J
%A Lu Q
%A Kang L
%A Zheng SR
%A Li J
%A Cao S
%A Das C
%A Liu X
%A Song L
%A Ouyang S
%A Luo ZQ
%J Res Sq
%V 0
%N 0
%D 2024 May 20
%M 38826349
暂无%R 10.21203/rs.3.rs-4431542/v1
%X The reversal of ubiquitination induced by members of the SidE effector family of Legionella pneumophila produces phosphoribosyl ubiquitin (PR-Ub) that is potentially detrimental to host cells. Here we show that the effector LnaB functions to transfer the AMP moiety from ATP to the phosphoryl moiety of PR-Ub to convert it into ADP-ribosylated ubiquitin (ADPR-Ub), 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 (S-HxxxE) present in a large family of toxins from diverse bacterial pathogens. Our study not only reveals intricate mechanisms for a pathogen to maintain ubiquitin homeostasis but also identifies a new family of enzymes capable of protein AMPylation, suggesting that this posttranslational modification is widely used in signaling during host-pathogen interactions.