LotA, a Legionella deubiquitinase, has dual catalytic activity and contributes to intracellular growth

Abstract The intracellular bacterial pathogen Legionella pneumophila establishes the replicative niche as a result of the actions of a large array of effector proteins delivered via the Legionella type IV secretion system (T4SS). Many effector proteins are expected to be involved in biogenesis and regulation of the Legionella‐containing vacuole (LCV) that is highly decorated with ubiquitin. Here, we identified a Legionella deubiquitinase (DUB), designated LotA, by carrying out a genome analysis to find proteins resembling the eukaryotic ovarian tumor (OTU) superfamily of cysteine proteases. LotA exhibits a dual ability to cleave ubiquitin chains that is dependent on two distinctive catalytic cysteine residues in the OTU domains. One cysteine dominantly contributes to the removal of ubiquitin from the LCVs by its polyubiquitin cleavage activity. The other specifically cleaves conjugated Lys6‐linked ubiquitin. After delivered by the T4SS, LotA localizes on the LCVs via its PI(3)P‐binding domain. The lipid‐binding ability of LotA is crucial for ubiquitin removal from the vacuoles. We further analyzed the functional interaction of the protein with the recently reported noncanonical ubiquitin ligases of L. pneumophila, revealing that the effector proteins are involved in coordinated regulation that contributes to bacterial growth in the host cells.
Source: Cellular Microbiology - Category: Microbiology Authors: Tags: RESEARCH ARTICLE Source Type: research