A bifunctional enzyme of Legionella that distinctly regulates phosphoribosyl ubiquitination of the SidE family effectors

[摘要] Legionella pneumophila is a Gram-negativeintracellular pathogen that can replicatewithin freshwater amoeba and mammalianalveolar macrophages. In order to establishan intracellular niche permissive for itsreplication, Legionella translocates over300 different effector proteins into thehost cytosol via its Dot/Icm secretionsystem.[1] Among these, members ofthe SidE effector family (SidE, SdeA,SdeB, and SdeC) regulate multiple cellularprocesses by a unique phosphoribosyl (PR)ubiquitination mechanism that bypassesthe canonical ubiquitination machinery,[1]and two phosphoglycosyl ubiquitin (PRUb)-specific deubiquitinases of Legionella(DupA and DupB) could cleave the PR-Ubinduced by SidEs from PR-ubiquitinatedsubstrates. The activity of the SidE family isregulated by a calmodulin (CaM)-dependentglutamylase effector of Legionella, namedSidJ. Activated SidJ inhibits the adenosinediphosphate (ADP)-ribotransferase activityof SidEs by covalently attaching oneor more glutamate moieties on the firstglutamate residue of the ExE (where “x”represents any amino acid) element of themono-ADP-ribosyl transferase (mART)domain that is essential for ubiquitinactivation.[2,3] Interestingly, SdjA, a memberof SidJ family in some Legionella strains,shares high level of sequence and structuralidentities to SidJ.[4] However, the functionof SdjA is still unknown.