Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes

Liu, Shuxin; Luo, Jiwei; Zhen, Xiangkai; Qiu, Jiazhang; Ouyang, Songying; Luo, Zhao‐Qing

doi:10.7554/elife.58114

Cited by 45 publications

(68 citation statements)

References 70 publications

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“…S4F ). Based on the Ub- and diUb-bound structures of LotC and LotA N , respectively, it is the unique features of the α1-2 region that dictate interactions to Ub (Liu et al , 2020) ( Fig. S4F-H ).…”

Section: Resultsmentioning

confidence: 99%

Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA

Warren

Kitao

Franklin

et al. 2022

Preprint

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The versatility of ubiquitination to impose control over vast domains of eukaryotic biology is due, in part, to diversification through differently-linked poly-ubiquitin chains. Deciphering the signaling roles for some poly-ubiquitin chain types, including those linked via K6, has been stymied by a lack of stringent linkage specificity among the implicated regulatory proteins. Forged through strong evolutionary pressures, pathogenic bacteria have evolved intricate mechanisms to regulate host ubiquitin, and in some cases even with exquisite specificity for distinct poly-ubiquitin signals. Herein, we identify and characterize a deubiquitinase domain of the secreted effector protein LotA from Legionella pneumophila that specifically regulates K6-linked poly-ubiquitin during infection. We demonstrate the utility of LotA as a tool for studying K6 poly-ubiquitin. By determining apo and diUb-bound structures, we identify the mechanism of LotA activation and K6 poly-ubiquitin specificity, and identify a novel ubiquitin-binding domain utilized among bacterial deubiquitinases.

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Section: Resultsmentioning

confidence: 99%

Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA

Warren

Kitao

Franklin

et al. 2022

Preprint

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“…Notably, L. pneumophila produces the DUB effector Lem27/LotC, a eukaryotic-like cysteine protease related to the ovarian tumour (OTU) superfamily, which removes the modification, suggesting that the PTM is employed to temporarily manipulate the function of the Rabs [207–209].…”

Section: Dot/icm T4bss Effectorsmentioning

confidence: 99%

The Legionella pneumophila Dot/Icm type IV secretion system and its effectors

et al. 2022

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To prevail in the interaction with eukaryotic hosts, many bacterial pathogens use protein secretion systems to release virulence factors at the host–pathogen interface and/or deliver them directly into host cells. An outstanding example of the complexity and sophistication of secretion systems and the diversity of their protein substrates, effectors, is the Defective in organelle trafficking/Intracellular multiplication (Dot/Icm) Type IVB secretion system (T4BSS) of Legionella pneumophila and related species. Legionella species are facultative intracellular pathogens of environmental protozoa and opportunistic human respiratory pathogens. The Dot/Icm T4BSS translocates an exceptionally large number of effectors, more than 300 per L. pneumophila strain, and is essential for evasion of phagolysosomal degradation and exploitation of protozoa and human macrophages as replicative niches. Recent technological advancements in the imaging of large protein complexes have provided new insight into the architecture of the T4BSS and allowed us to propose models for the transport mechanism. At the same time, significant progress has been made in assigning functions to about a third of L. pneumophila effectors, discovering unprecedented new enzymatic activities and concepts of host subversion. In this review, we describe the current knowledge of the workings of the Dot/Icm T4BSS machinery and provide an overview of the activities and functions of the to-date characterized effectors in the interaction of L. pneumophila with host cells.

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“…Interestingly, ubiquitination and recruitment of Rab10 to the LCV by SidC and SdcA are regulated by a third OUT-like Dub Lem27 (Lpg2529) (also known as LotC) coded for by L. pneumophila ( Schubert et al, 2020 ; Shin et al, 2020a ). Lem27 appears to modulate Rab10 ubiquitination by counteracting the activity of SidC and SdcA ( Liu et al, 2020 ). Ceg7 (Lpg0227) has also been shown to possess Dub activity and belongs to the OUT-like family ( Hermanns et al, 2020 ; Schubert et al, 2020 ).…”

Section: Dubsmentioning

confidence: 99%

Exploitation of the Host Ubiquitin System: Means by Legionella pneumophila

et al. 2021

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Ubiquitination is a commonly used post-translational modification (PTM) in eukaryotic cells, which regulates a wide variety of cellular processes, such as differentiation, apoptosis, cell cycle, and immunity. Because of its essential role in immunity, the ubiquitin network is a common target of infectious agents, which have evolved various effective strategies to hijack and co-opt ubiquitin signaling for their benefit. The intracellular pathogen Legionella pneumophila represents one such example; it utilizes a large cohort of virulence factors called effectors to modulate diverse cellular processes, resulting in the formation a compartment called the Legionella-containing vacuole (LCV) that supports its replication. Many of these effectors function to re-orchestrate ubiquitin signaling with distinct biochemical activities. In this review, we highlight recent progress in the mechanism of action of L. pneumophila effectors involved in ubiquitination and discuss their roles in bacterial virulence and host cell biology.

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Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes

Cited by 45 publications

References 70 publications

Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA

Mechanism of Lys6 poly-ubiquitin specificity by the L. pneumophila deubiquitinase LotA

The Legionella pneumophila Dot/Icm type IV secretion system and its effectors

Exploitation of the Host Ubiquitin System: Means by Legionella pneumophila

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