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Ubiquitination of Sec22b by a novel Legionella pneumophila ubiquitin E3 ligase

is a facultative intracellular pathogen that causes legionellosis. The key to its virulence is the delivery of hundreds of effector proteins into host cells via the efective in rganelle rafficking/ ntra ellular ultiplication type IV secretion system. These effectors modulate numerous host signaling...

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Bibliographic Details
Published in:mBio 2023-12, Vol.14 (6), p.e0238223
Main Authors: Ma, Kelong, Shu, Rundong, Liu, Hongtao, Fu, Jiaqi, Luo, Zhao-Qing, Qiu, Jiazhang
Format: Article
Language:English
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Summary:is a facultative intracellular pathogen that causes legionellosis. The key to its virulence is the delivery of hundreds of effector proteins into host cells via the efective in rganelle rafficking/ ntra ellular ultiplication type IV secretion system. These effectors modulate numerous host signaling pathways to create a niche called the - ontaining acuole (LCV) permissive for its intracellular replication. Previous investigation revealed that exploitation of the host ubiquitin system is among the most important strategies used by to coopt host processes for its benefit. Here, we show that the effector ubiquitin ligase gene 15 (Lug15) (Lpg2327), which has no detectable homology with any enzyme involved in ubiquitin signaling, is an E3 ligase. In -infected cells, Lug15 is localized on the LCV and impacts its association with polyubiquitinated proteins. We also demonstrate that Sec22b is ubiquitinated and recruited to the LCV by Lug15. Thus, our results establish Lug15 as a novel E3 ligase that functions to recruit a SNARE protein to remodel the phagosome.IMPORTANCEProtein ubiquitination is one of the most important post-translational modifications that plays critical roles in the regulation of a wide range of eukaryotic signaling pathways. Many successful intracellular bacterial pathogens can hijack host ubiquitination machinery through the action of effector proteins that are injected into host cells by secretion systems. is the etiological agent of legionellosis that is able to survive and replicate in various host cells. The efective in rganelle rafficking (Dot)/ ntra ellular ultiplication (Icm) type IV secretion system of injects over 330 effectors into infected cells to create an optimal environment permissive for its intracellular proliferation. To date, at least 26 Dot/Icm substrates have been shown to manipulate ubiquitin signaling via diverse mechanisms. Among these, 14 are E3 ligases that either cooperate with host E1 and E2 enzymes or adopt E1/E2-independent catalytic mechanisms. In the present study, we demonstrate that the effector ubiquitin ligase gene 15 (Lug15) is a novel ubiquitin E3 ligase. Lug15 is involved in the remodeling of LCV with polyubiquitinated species. Moreover, Lug15 catalyzes the ubiquitination of host SNARE protein Sec22b and mediates its recruitment to the LCV. Ubiquitination of Sec22b by Lug15 promotes its noncanonical pairing with plasma membrane-derived syntaxins (e.g., Stx3). Our study further reveals the complexity of st
ISSN:2150-7511
2150-7511
DOI:10.1128/mbio.02382-23