Legionella pneumophila temporally regulates the activity of ADP/ATP translocases by reversible ADP-ribosylation  

作　　者：Jiaqi Fu Pengwei Li Hongxin Guan Dan Huang Lei Song Songying Ouyang Zhao-Qing Luo 

机构地区：[1]Department of Biological Sciences,Purdue Institute for Inflammation,Immunology and Infectious Disease,Purdue University,West Lafayette,Indiana,USA [2]Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation,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,Fuzhou,China [3]Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education,State Key Laboratory of Zoonotic Diseases,Department of Respiratory Medicine,Center for Pathogen Biology and Infectious Diseases,The First Hospital of Jilin University,Changchun,China

出　　处：《mLife》2022年第1期51-65,共15页微生物（英文）

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);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).

摘　　要：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.

关 键 词：energy metabolism metaeffector MITOCHONDRIA type IV secretion 

分 类 号：Q93[生物学—微生物学]