학술논문
Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N
Document Type
Original Paper
Source
Nature Microbiology. 4(1):134-143
Subject
Language
English
ISSN
2058-5276
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-κB 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.
A Legionella pneumophila effector, MavC, mediates ubiquitination through a transglutamination reaction and targets host UBE2N to inhibit immune signalling during infection.
A Legionella pneumophila effector, MavC, mediates ubiquitination through a transglutamination reaction and targets host UBE2N to inhibit immune signalling during infection.