January 12, 2022
Journal Article

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

Abstract

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

Citation

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

Research topics