Bacterial pseudokinase catalyzes protein polyglutamylation to inhibit the SidE-family ubiquitin ligases

Abstract

Divergent protein kinase SidJ is a protein produced by Legionella pneumophila that orchestrates this intracellular pathogen's establishment within the host cell. SidJ prevents lysosome fusion with the vacuole, within which the bacterium resides and replicates. SidJ also modulates the toxicity of the SidE family ubiquitin ligases that catalyze phosphoribosyl-linked host protein ubiquitination. Black et al. discovered that SidJ is activated by host calmodulin. Furthermore, although SidJ has a pseudokinase fold, it does not phosphorylate SidE proteins but polyglutamylates them instead. The in vivo relevance of this mechanism for bacterial infectivity was verified in the natural reservoir host Acanthamoeba castellanii . Science , this issue p. 787