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Title: Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N

Abstract

The bacterial pathogen Legionella pneumophila modulates host immunity using effectors translocated by its Dot/Icm transporter to facilitate its intracellular replication. A number of these effectors employ diverse mechanisms to interfere with protein ubiquitination, a post-translational modification essential for immunity. Here, we have found that L. pneumophila induces monoubiquitination of the E2 enzyme UBE2N by its Dot/Icm substrate MavC(Lpg2147). We demonstrate that MavC is a transglutaminase that catalyses covalent linkage of ubiquitin to Lys92 and Lys94 of UBE2N via Gln40. Similar to canonical transglutaminases, MavC possess deamidase activity that targets ubiquitin at Gln40. We identified Cys74 as the catalytic residue for both ubiquitination and deamidation activities. Furthermore, ubiquitination of UBE2N by MavC abolishes its activity in the formation of K63-type polyubiquitin chains, which dampens NF-? B signalling in the initial phase of bacterial infection. Our results reveal an unprecedented mechanism of modulating host immunity by modifying a key ubiquitination enzyme by ubiquitin transglutamination.

Authors:
ORCiD logo; ORCiD logo; ; ORCiD logo
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1496611
Report Number(s):
PNNL-SA-129705
Journal ID: ISSN 2058-5276
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Nature Microbiology
Additional Journal Information:
Journal Volume: 4; Journal Issue: 1; Journal ID: ISSN 2058-5276
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

Citation Formats

Gan, Ninghai, Nakayasu, Ernesto S., Hollenbeck, Peter J., and Luo, Zhao-Qing. Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N. United States: N. p., 2018. Web. doi:10.1038/s41564-018-0282-8.
Gan, Ninghai, Nakayasu, Ernesto S., Hollenbeck, Peter J., & Luo, Zhao-Qing. Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N. United States. doi:10.1038/s41564-018-0282-8.
Gan, Ninghai, Nakayasu, Ernesto S., Hollenbeck, Peter J., and Luo, Zhao-Qing. Mon . "Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N". United States. doi:10.1038/s41564-018-0282-8.
@article{osti_1496611,
title = {Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N},
author = {Gan, Ninghai and Nakayasu, Ernesto S. and Hollenbeck, Peter J. and Luo, Zhao-Qing},
abstractNote = {The bacterial pathogen Legionella pneumophila modulates host immunity using effectors translocated by its Dot/Icm transporter to facilitate its intracellular replication. A number of these effectors employ diverse mechanisms to interfere with protein ubiquitination, a post-translational modification essential for immunity. Here, we have found that L. pneumophila induces monoubiquitination of the E2 enzyme UBE2N by its Dot/Icm substrate MavC(Lpg2147). We demonstrate that MavC is a transglutaminase that catalyses covalent linkage of ubiquitin to Lys92 and Lys94 of UBE2N via Gln40. Similar to canonical transglutaminases, MavC possess deamidase activity that targets ubiquitin at Gln40. We identified Cys74 as the catalytic residue for both ubiquitination and deamidation activities. Furthermore, ubiquitination of UBE2N by MavC abolishes its activity in the formation of K63-type polyubiquitin chains, which dampens NF-? B signalling in the initial phase of bacterial infection. Our results reveal an unprecedented mechanism of modulating host immunity by modifying a key ubiquitination enzyme by ubiquitin transglutamination.},
doi = {10.1038/s41564-018-0282-8},
journal = {Nature Microbiology},
issn = {2058-5276},
number = 1,
volume = 4,
place = {United States},
year = {2018},
month = {11}
}