The Legionella Effector SdjA Is a Bifunctional Enzyme That Distinctly Regulates Phosphoribosyl Ubiquitination

Song, Lei; Xie, Yongchao; Li, Chuang; Wang, Lidong; He, Chunlin; Zhang, Yong; Yuan, Jingya; Luo, Jingjing; Liu, Xi; Xiu, Yu; Li, Hang; Gritsenko, Marina A.; Nakayasu, Ernesto S.; Feng, Yue; Luo, Zhao-Qing

doi:10.1128/mbio.02316-21

The Legionella Effector SdjA Is a Bifunctional Enzyme That Distinctly Regulates Phosphoribosyl Ubiquitination

Journal Article · Tue Sep 07 00:00:00 EDT 2021 · mBio (Online)

DOI:https://doi.org/10.1128/mbio.02316-21· OSTI ID:1839080

Song, Lei ^[1]; Xie, Yongchao ^[2]; Li, Chuang ^[3]; Wang, Lidong ^[1]; He, Chunlin ^[1]; Zhang, Yong ^[1]; Yuan, Jingya ^[1]; Luo, Jingjing ^[1]; Liu, Xi ^[2]; Xiu, Yu ^[2]; Li, Hang ^[2]; ^[4]; ^[4]; Feng, Yue ^[2]; Luo, Zhao-Qing ^[3]

Jilin Univ., Changchun (China)
Beijing Univ. of Chemical Technology (China)
Purdue Univ., West Lafayette, IN (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

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), which is 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 and 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 from 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. Our results reveal that an enzyme can catalyze two completely opposite biochemical reactions, which highlights the distinct regulation of phosphoribosyl ubiquitination by the SidJ effector family.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1839080

Report Number(s):: PNNL-SA--166276

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 5 Vol. 12; ISSN 2150-7511

Publisher:: American Society for Microbiology (ASM)Copyright Statement

Country of Publication:: United States

Language:: English

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