Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection DOI Creative Commons
Yaobin Liu, Rukmini Mukherjee,

Florian Bonn

и другие.

Cell Death and Differentiation, Год журнала: 2021, Номер 28(10), С. 2957 - 2969

Опубликована: Июль 20, 2021

Abstract SidE family of Legionella effectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) host proteins during bacterial infection. SdeA localizes predominantly to ER and partially the Golgi apparatus, mediates serine multiple proteins. Here we show that causes disruption integrity due its ubiquitin ligase activity. The linking GRASP55 GRASP65 are PR-ubiquitinated on residues, thus preventing their ability cluster form oligomeric structures. In addition, found functional consequence is not linked recruitment membranes growing -containing vacuoles. Instead, it affects secretory pathway. Taken together, our study sheds light manipulation strategy by which hijacks pathway promotes

Язык: Английский

Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain DOI Creative Commons
Zhengrui Zhang, Jiaqi Fu, J.G.M. Rack

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 19, 2024

Abstract ADP-ribosylation is a reversible post-translational modification involved in various cellular activities. Removal of requires (ADP-ribosyl)hydrolases, with macrodomain enzymes being major family this category. The pathogen Legionella pneumophila mediates atypical ubiquitination host targets using the SidE effector process that involves ubiquitin on arginine 42 as an obligatory step. Here, we show MavL regulates pathway by reversing ADP-ribosylation, likely to minimize potential detrimental effects caused modified ubiquitin. We determine crystal structure ADP-ribose-bound MavL, providing structural insights into recognition ADP-ribosyl group and catalytic mechanism its removal. Further analyses reveal DUF4804 class MavL-like whose representative members unique selectivity for mono-ADP-ribosylated residue synthetic substrates. find such are also present eukaryotes, exemplified two previously uncharacterized (ADP-ribosyl)hydrolases Drosophila melanogaster . Crystal structures several proteins provide specificity shared mode ADP-ribose interaction distinct from characterized macrodomains. Collectively, our study reveals new regulatory layer SidE-catalyzed expands current understanding enzymes.

Язык: Английский

Процитировано

6
Phosphoribosyl modification of poly-ubiquitin chains at the Legionella-containing vacuole prohibiting autophagy adaptor recognition DOI Creative Commons
Min Wan, Marena E. Minelli, Qiuye Zhao

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 30, 2024

Ubiquitination is a posttranslational modification in eukaryotes that plays significant role the infection of intracellular microbial pathogens, such as Legionella pneumophila. While Legionella-containing vacuole (LCV) coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. Here, we report Sdc and Sde families effectors work together to build ubiquitinated species around LCV. The catalyze canonical polyubiquitination directly on host targets or phosphoribosyl-Ub conjugated Sde. Remarkably, Ub moieties within poly-Ub chains are either modified phosphoribosyl group PDE domain-containing covalently attached other substrates via Sde-mediated phosphoribosyl-ubiquitination. Furthermore, these modifications prevent adaptors therefore exclude from In this work, shed light nature poly-ubiquitinated present at surface LCV provide molecular mechanism for avoidance Ub-decorated

Язык: Английский

Процитировано

6
Divergence of Legionella Effectors Reversing Conventional and Unconventional Ubiquitination DOI Creative Commons
Tomoe Kitao, Hiroki Nagai, Tomoko Kubori

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2020, Номер 10

Опубликована: Авг. 21, 2020

The intracellular bacterial pathogen Legionella pneumophila employs bacteria-derived effector proteins in a variety of functions to exploit host cellular systems. ubiquitination machinery constitutes crucial eukaryotic system for the regulation numerous processes and is representative target effector-mediated manipulation. L. transports more than 300 into cells through type IV secretion system. Among these, several have been found function as ubiquitin ligases, including unprecedented enzymes that catalyze unconventional mechanisms. Recent studies identified many can interfere ubiquitination. These effectors include are distantly related ovarian tumor protein superfamily described deubiquitinases (DUBs), which regulate important signaling cascades human cells. Intriguingly, DUBs not limited exhibit canonical DUB activity. Some cleavage linkage substrates. Furthermore, novel mechanisms adversely affect specific ligases; instance, an posttranslational modification ligases results inhibition their Bacterial inhibit ligase activity, cognate DUBs, examples effector/metaeffector sets due opposing functional relationship. In context infection, existence reverse mainly relates fine tuning biogenesis remodeling Legionella-containing vacuole replicative niche. complexity arrays reflects sophisticated strategies bacteria adopted adapt its environment enable survival This review summarizes current state knowledge on divergent ubiquitination, mediated by other well machinery.

Язык: Английский

Процитировано

37
Legionella hijacks the host Golgi-to-ER retrograde pathway for the association of Legionella-containing vacuole with the ER DOI Creative Commons

Mio Kawabata,

Honoka Matsuo,

Takumi Koito

и другие.

PLoS Pathogens, Год журнала: 2021, Номер 17(3), С. e1009437 - e1009437

Опубликована: Март 24, 2021

Legionella pneumophila ( L . ) is a gram-negative bacterium that replicates in compartment resembles the host endoplasmic reticulum (ER). To create its replicative niche, manipulates membrane traffic and fusion machineries. Bacterial proteins called effectors are translocated into cytosol play crucial role these processes. In an early stage of infection, subverts ER-derived vesicles (ERDVs) by manipulating GTPase Rab1 to facilitate remodeling -containing vacuole (LCV). Subsequently, LCV associates with ER mechanism remains elusive. this study, we show recruits GTPases Rab33B Rab6A, which regulate vesicle trafficking from Golgi ER, promote association ER. We found recruitment Rab6A depends on Rab33B. effector SidE family proteins, phosphoribosyl-ubiquitinate Rab33B, were be necessary for LCV. Immunoprecipitation experiments revealed facilitates interaction Rab6 ER-resident SNAREs comprising syntaxin 18, p31, BNIP1, but not tethering factors including NAG, RINT-1, ZW10, normally required 18-mediated Golgi-derived Our results identified Rab33B-Rab6A cascade SNARE disclosed unidentified physiological proteins.

Язык: Английский

Процитировано

32
Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection DOI Creative Commons
Yaobin Liu, Rukmini Mukherjee,

Florian Bonn

и другие.

Cell Death and Differentiation, Год журнала: 2021, Номер 28(10), С. 2957 - 2969

Опубликована: Июль 20, 2021

Abstract SidE family of Legionella effectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) host proteins during bacterial infection. SdeA localizes predominantly to ER and partially the Golgi apparatus, mediates serine multiple proteins. Here we show that causes disruption integrity due its ubiquitin ligase activity. The linking GRASP55 GRASP65 are PR-ubiquitinated on residues, thus preventing their ability cluster form oligomeric structures. In addition, found functional consequence is not linked recruitment membranes growing -containing vacuoles. Instead, it affects secretory pathway. Taken together, our study sheds light manipulation strategy by which hijacks pathway promotes

Язык: Английский

Процитировано

30