Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection DOI Creative Commons
Dong Hyuk Shin, Anshu Bhattacharya, Yi-Lin Cheng

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 13, 2020

Legionella pneumophila causes a severe pneumonia known as Legionnaires' disease. During the infection, injects more than 300 effector proteins into host cells. Among them are enzymes involved in altering host-ubiquitination system. Here, we identified two LegionellaOTU (ovarian tumor)-like deubiquitinases (LOT-DUBs; LotB [Lpg1621/Ceg23] and LotC [Lpg2529]). The crystal structure of catalytic core (LotC14-310) was determined at 2.4 Å. Unlike classical OTU-family, LOT-family shows an extended helical lobe between Cys-loop variable loop, which defines unique class OTU-DUBs. has additional ubiquitin-binding site (S1'), enables specific cleavage Lys63-linked polyubiquitin chains. By contrast, only contains S1 cleaves different species ubiquitin MS analysis categories host-interacting substrates. Together, our results provide new structural insights bacterial OTU-DUBs indicate distinct roles host-pathogen interactions.

Language: Английский

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

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(4), P. 273 - 287

Published: Oct. 25, 2022

Language: Английский

Citations

230
ER remodeling via ER-phagy DOI Creative Commons
Andrea Gubaš, Ivan Đikić

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(8), P. 1492 - 1500

Published: April 1, 2022

The endoplasmic reticulum (ER) is a hotspot for many essential cellular functions. ER membrane highly dynamic, which affects processes that take place within the ER. One such process ER-phagy, selective degradation of fragments (including membranes and luminal content), serves to preserve size while adapting its morphology under basal stress conditions. In order be degraded, undergoes fragmentation facilitated by specialized ER-shaping proteins also act as ER-phagy receptors. Their ability sense induce curvature, well bridge with autophagy machinery, allows successful delivery these lysosome recycling. this review, we provide insights into from perspective remodeling. We highlight importance dynamics during emphasize how dysregulation reflects on human physiology pathology.

Language: Английский

Citations

85
Ubiquitin—A structural perspective DOI
Rashmi Agrata, David Komander

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 323 - 346

Published: Jan. 1, 2025

Language: Английский

Citations

3
Outer membrane vesicles containing OmpA induce mitochondrial fragmentation to promote pathogenesis of Acinetobacter baumannii DOI Creative Commons
Varnesh Tiku, Eric M. Kofoed, Donghong Yan

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Jan. 12, 2021

Abstract Acinetobacter baumannii is a highly antibiotic resistant Gram-negative bacterium that causes life-threatening infections in humans with very high mortality rate. A. an extracellular pathogen poorly understood virulence mechanisms. Here we report employs the release of outer membrane vesicles (OMVs) containing protein A (OmpA Ab ) to promote bacterial pathogenesis and dissemination. OMVs OmpA are taken up by mammalian cells where they activate host GTPase dynamin-related 1 (DRP1). mediated activation DRP1 enhances its accumulation on mitochondria mitochondrial fragmentation, elevation reactive oxygen species (ROS) production cell death. Loss rescues these phenotypes. Our data show sufficient induce fragmentation cytotoxicity since expression E. coli transfers pathogenic properties . infection mice also induces damage alveolar macrophages dependent manner. We finally required for systemic dissemination mouse lung model. In this study uncover mechanism as factor further establish effects.

Language: Английский

Citations

74
A new dawn beyond lysine ubiquitination DOI

Daniel R. Squair,

Satpal Virdee

Nature Chemical Biology, Journal Year: 2022, Volume and Issue: 18(8), P. 802 - 811

Published: July 27, 2022

Language: Английский

Citations

60
Legionella pneumophila modulates host energy metabolism by ADP-ribosylation of ADP/ATP translocases DOI Creative Commons
Jiaqi Fu, Mowei Zhou, Marina Gritsenko

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 27, 2022

The intracellular pathogen Legionella pneumophila delivers more than 330 effectors into host cells by its Dot/Icm secretion system. Those direct the biogenesis of -containing vacuole (LCV) that permits survival and replication. It has long been documented LCV is associated with mitochondria a number have shown to target this organelle. Yet, biochemical function cell most these remain unknown. Here, we found substrate Ceg3 (Lpg0080) mono-ADP-ribosyltransferase localizes in where it attacks ADP/ATP translocases ADP-ribosylation, blunts their exchange activity. modification occurs on second arginine residue -RRRMMM- element, which conserved among all known carriers from different organisms. Our results reveal modulation energy metabolism as virulence mechanism for L. .

Language: Английский

Citations

45
Non-lysine ubiquitylation: Doing things differently DOI Creative Commons
Ian R. Kelsall

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 19, 2022

The post-translational modification of proteins with ubiquitin plays a central role in nearly all aspects eukaryotic biology. Historically, studies have focused on the conjugation to lysine residues substrates, but it is now clear that ubiquitylation can also occur cysteine, serine, and threonine residues, as well N-terminal amino group proteins. Paradigm-shifting reports non-proteinaceous substrates further extended reach beyond proteome include intracellular lipids sugars. Additionally, results from bacteria revealed novel ways ubiquitylate (and deubiquitylate) without need for any enzymatic components canonical cascade. Focusing mainly upon recent findings, this review aims outline current understanding non-lysine speculate molecular mechanisms physiological importance non-canonical modification.

Language: Английский

Citations

44
A lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins DOI
Anshu Bhattacharya, Rukmini Mukherjee, Santosh Kumar Kuncha

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(5), P. 685 - 698

Published: April 6, 2023

Language: Английский

Citations

42
The ubiquitin codes in cellular stress responses DOI Creative Commons

Xiangpeng Sheng,

Zhixiong Xia,

Hanting Yang

et al.

Protein & Cell, Journal Year: 2023, Volume and Issue: 15(3), P. 157 - 190

Published: July 19, 2023

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications, regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components numerous biological processes undergo ubiquitination mammalian cells upon exposure to diverse stresses, from exogenous factors reactions, causing a dazzling variety functional consequences. Various forms ubiquitin signals generated by ubiquitylation events specific milieus, known as codes, constitute an intrinsic part myriad stress responses. These events, leading proteolytic turnover substrates or just switch functionality, initiate, regulate, supervise multiple stress-associated responses, supporting adaptation, homeostasis recovery, and survival stressed cells. In this review, we attempted summarize crucial roles response different environmental intracellular while discussing how stresses modulate system. This review also updates recent advances understanding machinery well responses discusses some important questions may warrant future investigation.

Language: Английский

Citations

42
Non-proteolytic ubiquitylation in cellular signaling and human disease DOI Creative Commons
Yongrong Liao, Izabela Sumara, Evanthia Pangou

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: Feb. 8, 2022

Abstract Ubiquitylation is one of the most common post-translational modifications (PTMs) proteins that frequently targets substrates for proteasomal degradation. However it can also result in non-proteolytic events which play important functions cellular processes such as intracellular signaling, membrane trafficking, DNA repair and cell cycle. Emerging evidence demonstrates dysfunction ubiquitylation associated with development multiple human diseases. In this review, we summarize current knowledge latest concepts on how pathways are involved signaling disease-mediating processes. Our may advance our understanding non-degradative process.

Language: Английский

Citations

41