The mitochondrion is an important signaling hub that governs diverse cellular functions,including metabolism,energy production,and immunity.Among the hundreds of effectors translocated into host cells by the Dot/Icm s...The mitochondrion is an important signaling hub that governs diverse cellular functions,including metabolism,energy production,and immunity.Among the hundreds of effectors translocated into host cells by the Dot/Icm system of Legionella pneumophila,several are targeted to mitochondria but the function of most of them remains elusive.Our recent study found that the effector Ceg3 inhibits the activity of ADP/ATP translocases(ANTs)by ADP-ribosylation(ADPR).Here,we show that the effect of Ceg3 is antagonized by Larg1,an effector encoded by lpg0081,a gene that is situated next to ceg3.Larg1 functions to reverse Ceg3-mediated ADPR of ANTs by cleaving the N-glycosidic bond between the ADPR moiety and the modified arginine residues in ANTs,leading to restoration of their activity in ADP/ATP exchange.Structural analysis of Larg1 and its complex with ADPR reveals that this ADPR glycohydrolase harbors a unique macrodomain that catalyzes the removal of ADPR modification on ANTs.Our results also demonstrate that together with Ceg3,Larg1 imposes temporal regulation of the activity of ANTs by reversible ADPR during L.pneumophila infection.展开更多
基金supported by National Institutes of Health grant R01AI127465(Zhao-Qing Luo)the National Nature Science Foundation of China grants 82172287,31770948(Songying Ouyang)and 32171265(Hongxin Guan)+1 种基金the Fujian Provincial Department of Science and Technology(2020Y4007,2021H0004)(Songying Ouyang)the High-level personnel introduction grant of Fujian Normal University(Z0210509)(Songying Ouyang).
文摘The mitochondrion is an important signaling hub that governs diverse cellular functions,including metabolism,energy production,and immunity.Among the hundreds of effectors translocated into host cells by the Dot/Icm system of Legionella pneumophila,several are targeted to mitochondria but the function of most of them remains elusive.Our recent study found that the effector Ceg3 inhibits the activity of ADP/ATP translocases(ANTs)by ADP-ribosylation(ADPR).Here,we show that the effect of Ceg3 is antagonized by Larg1,an effector encoded by lpg0081,a gene that is situated next to ceg3.Larg1 functions to reverse Ceg3-mediated ADPR of ANTs by cleaving the N-glycosidic bond between the ADPR moiety and the modified arginine residues in ANTs,leading to restoration of their activity in ADP/ATP exchange.Structural analysis of Larg1 and its complex with ADPR reveals that this ADPR glycohydrolase harbors a unique macrodomain that catalyzes the removal of ADPR modification on ANTs.Our results also demonstrate that together with Ceg3,Larg1 imposes temporal regulation of the activity of ANTs by reversible ADPR during L.pneumophila infection.
