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

Post-translational regulation of ubiquitin signaling DOI Creative Commons
Lei Song, Zhao‐Qing Luo

The Journal of Cell Biology, Год журнала: 2019, Номер 218(6), С. 1776 - 1786

Опубликована: Апрель 18, 2019

Ubiquitination regulates many essential cellular processes in eukaryotes. This post-translational modification (PTM) is typically achieved by E1, E2, and E3 enzymes that sequentially catalyze activation, conjugation, ligation reactions, respectively, leading to covalent attachment of ubiquitin, usually lysine residues substrate proteins. Ubiquitin can also be successively linked one the seven on ubiquitin form distinctive forms polyubiquitin chains, which, depending upon used length dictate fate Recent discoveries revealed this code further expanded PTMs such as phosphorylation, acetylation, deamidation, ADP-ribosylation, components ubiquitination machinery, or both. These provide additional regulatory nodes integrate development insulting signals with homeostasis. Understanding precise roles these regulation signaling will new insights into mechanisms treatment various human diseases ubiquitination, including neurodegenerative diseases, cancer, infection, immune disorders.

Язык: Английский

Процитировано

276

An expanded lexicon for the ubiquitin code DOI Open Access
Ivan Ðikić, Brenda A. Schulman

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 24(4), С. 273 - 287

Опубликована: Окт. 25, 2022

Язык: Английский

Процитировано

230

Ubiquitin—A structural perspective DOI
Rashmi Agrata, David Komander

Molecular Cell, Год журнала: 2025, Номер 85(2), С. 323 - 346

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

3

Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases DOI Open Access
Miles H. Black, Adam Osinski, Marcin Gradowski

и другие.

Science, Год журнала: 2019, Номер 364(6442), С. 787 - 792

Опубликована: Май 23, 2019

Divergent protein kinase SidJ is a produced by Legionella pneumophila that orchestrates this intracellular pathogen's establishment within the host cell. prevents lysosome fusion with vacuole, which bacterium resides and replicates. also modulates toxicity of SidE family ubiquitin ligases catalyze phosphoribosyl-linked ubiquitination. Black et al. discovered activated calmodulin. Furthermore, although has pseudokinase fold, it does not phosphorylate proteins but polyglutamylates them instead. The in vivo relevance mechanism for bacterial infectivity was verified natural reservoir Acanthamoeba castellanii . Science , issue p. 787

Язык: Английский

Процитировано

135

Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB DOI Creative Commons
Dong Hyuk Shin, Rukmini Mukherjee, Yaobin Liu

и другие.

Molecular Cell, Год журнала: 2019, Номер 77(1), С. 164 - 179.e6

Опубликована: Ноя. 12, 2019

The family of bacterial SidE enzymes catalyzes non-canonical phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity Legionella pneumophila. Here, we describe identification two effectors that reverse PR are thus named deubiquitinases for (DUPs; DupA DupB). Structural analyses revealed ubiquitin ligases harbor a highly homologous catalytic phosphodiesterase (PDE) domain. However, unlike ligases, displays increased affinity to PR-ubiquitinated substrates, which allows cleave from substrates. Interfering with DupA-ubiquitin binding switches its activity toward SidE-type ligase. Given the high exploited catalytically inactive mutant trap identify more than 180 host proteins in Legionella-infected cells. Proteins involved endoplasmic reticulum (ER) fragmentation membrane recruitment Legionella-containing vacuoles (LCV) emerged as major targets. global map substrates provides critical insights into host-pathogen interactions during infection.

Язык: Английский

Процитировано

121

Inhibition of bacterial ubiquitin ligases by SidJ–calmodulin catalysed glutamylation DOI
Sagar Bhogaraju,

Florian Bonn,

Rukmini Mukherjee

и другие.

Nature, Год журнала: 2019, Номер 572(7769), С. 382 - 386

Опубликована: Июль 22, 2019

Язык: Английский

Процитировано

118

Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase DOI
Ninghai Gan, Xiangkai Zhen, Yao Liu

и другие.

Nature, Год журнала: 2019, Номер 572(7769), С. 387 - 391

Опубликована: Июль 22, 2019

Язык: Английский

Процитировано

113

Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector DOI
Anıl Aktürk, David J. Wasilko, Xiaochun Wu

и другие.

Nature, Год журнала: 2018, Номер 557(7707), С. 729 - 733

Опубликована: Май 1, 2018

Язык: Английский

Процитировано

87

Deubiquitination of phosphoribosyl-ubiquitin conjugates by phosphodiesterase-domain–containingLegionellaeffectors DOI Open Access
Min Wan, Alan Sulpizio, Anıl Aktürk

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2019, Номер 116(47), С. 23518 - 23526

Опубликована: Ноя. 5, 2019

Posttranslational protein modification by ubiquitin (Ub) is a central eukaryotic mechanism that regulates plethora of physiological processes. Recent studies unveiled an unconventional type ubiquitination mediated the SidE family Legionella pneumophila effectors, such as SdeA, catalyzes conjugation Ub to serine residue target proteins via phosphoribosyl linker (hence named PR-ubiquitination). Comparable deubiquitinases in canonical pathway, here we show 2 paralogous Lpg2154 (DupA; deubiquitinase for PR-ubiquitination) and Lpg2509 (DupB), reverse PR-ubiquitination specific removal phosphoribosyl-Ub from substrates. Both DupA DupB are fully capable rescuing Golgi fragmentation phenotype caused exogenous expression SdeA mammalian cells. We further deletion these genes results significant accumulation PR-ubiquitinated species host cells infected with In addition, have identified list targets play role modulating association Legionella-containing vacuoles. Together, our data establish complete deubiquitination cycle demonstrate intricate control has over this unusual Ub-dependent posttranslational modification.

Язык: Английский

Процитировано

85

A new dawn beyond lysine ubiquitination DOI

Daniel R. Squair,

Satpal Virdee

Nature Chemical Biology, Год журнала: 2022, Номер 18(8), С. 802 - 811

Опубликована: Июль 27, 2022

Язык: Английский

Процитировано

61