January 12, 2022
Journal Article

The Legionella effector SdjA is a bifunctional enzyme that distinctly regulates phosphoribosyl ubiquitination


Legionella pneumophila promotes its survival and replication in phagocytes by actively modulating cellular processes using effectors injected into host cells by its Dot/Icm type IV secretion system. Many of these effectors function to manipulate the ubiquitin network of infected cells, thus contributing to the biogenesis of the Legionella-containing vacuole (LCV) permissive for bacterial replication. Among these, members of the SidE effector family (SidEs) catalyze ubiquitination of functionally diverse host proteins by a mechanism that is chemically distinct from the canonical three-enzyme cascade. The activity of SidEs is regulated by two mechanisms: reversal of the phosphoribosyl ubiquitination by DupA and DupB, as well as direct inactivation by SidJ, which is a calmodulin-dependent glutamylase. In many L. pneumophila strains, SidJ belongs to a two-member protein family. Its homolog SdjA appears to function differently to SidJ despite the high-level similarity in their primary sequences. Here we found that SdjA is a bifunctional enzyme that exhibits distinct activities toward members of the SidE family. It inhibits the activity of SdeB and SdeC by glutamylation. Unexpectedly, it also functions as a deglutamylase that reverses SidJ-induced glutamylation on SdeA, and to a less extent SidE. Our results reveal that an enzyme can catalyze two completely opposite biochemical reactions, which may have great implications in the study of protein evolution.

Published: January 12, 2022


Song L., Y. Xie, C. Li, L. Wang, C. He, Y. Zhang, and J. Yuan, et al. 2021. "The Legionella effector SdjA is a bifunctional enzyme that distinctly regulates phosphoribosyl ubiquitination." mBio 12, no. 5:e02316-21. PNNL-SA-166276. doi:10.1128/mBio.02316-21

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