<p>The bacterial pathogen <i>Legionella
pneumophila</i> 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 <i>L. pneumophila</i> induces monoubiquitination of the E2
enzyme UBE2N by its Dot/Icm substrate MavC(Lpg2147). Ubiquitination of UBE2N by
MavC abolishes its activity in the formation of K63-linked polyubiquitin
chains, which dampens NF-kB signaling in the initial phase of bacterial infection. The inhibition
of UBE2N activity by MavC creates a conundrum because this E2 enzyme is
important in multiple signaling pathways, including some that are important for
intracellular <i>L. pneumophila</i> replication. Here we also show that the
activity of UBE2N is restored by MvcA(Lpg2148), an ortholog of MavC. MvcA
functions to deubiquitinate UBE2N-Ub using the same catalytic triad required
for its deamidase activity. Structural analysis of the MvcA-UBE2N-Ub complex
reveals a crucial role of the insertion domain in MvcA in substrate
recognition. Our findings reveal that two remarkably similar proteins catalyze
the forward and reverse reactions to impose temporal regulation of the activity
of UBE2N during <i>L. pneumophila</i> infection.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/8980049 |
| Date | 13 August 2019 |
| Creators | Ninghai Gan (7023128) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/MODULATION_OF_THE_HOST_UBIQUITIN_MACHINERY_BY_LEGIONELLA_PNEUMOPHILA_EFFECTORS/8980049 |
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