Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase

Gan, Ninghai; Zhen, Xiangkai; Liu, Yao; Xu, Xiaolong; He, Chunlin; Qiu, Jiazhang; Liu, Yancheng; Fujimoto, Grant M.; Nakayasu, Ernesto S.; Zhou, Biao; Zhao, Lan; Puvar, Kedar; Das, Chittaranjan; Ouyang, Songying; Luo, Zhao-Qing

doi:10.1038/s41586-019-1439-1

Title: Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase

Journal Article · Thu Aug 15 00:00:00 EDT 2019 · Nature

DOI:https://doi.org/10.1038/s41586-019-1439-1· OSTI ID:1572484

Gan, Ninghai ^[1]; Zhen, Xiangkai ^[2]; Liu, Yao ^[1]; Xu, Xiaolong ^[2]; He, Chunlin ^[3]; Qiu, Jiazhang ^[3]; Liu, Yancheng ^[1]; Fujimoto, Grant M. ^[4];

^[4]; Zhou, Biao ^[2]; Zhao, Lan ^[2]; Puvar, Kedar ^[1]; Das, Chittaranjan ^[1]; Ouyang, Songying ^[2]; Luo, Zhao-Qing ^[1]

Purdue University
Fujian Normal University
Jilin University
BATTELLE (PACIFIC NW LAB)

The bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating the function of host cells using hundreds of effector proteins delivered via its Dot/Icm secretion system1. Among these, members of the SidE family (SidEs) regulate multiple cellular processes by a unique phosphoribosyl ubiquitination mechanism that bypasses the requirement of ATP and the E1, E2 enzymes of the canonical ubiquitination machinery2-4. The activity of SidEs is regulated by SidJ, another Dot/Icm effector5, but the mechanism of such regulation is not completely understood6,7. Here we demonstrate that SidJ functions to inhibit the activity of SidEs by inducing covalent attachment of a glutamate moiety to Glu860 of SdeA, which is one of the catalytic residues for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation2. Furthermore, we found that the inhibition of SidEs activity by SidJ is restricted in host cells and such spatial regulation is achieved by the requirement of calmodulin (CaM), a eukaryote-specific protein, for its activity. Our results reveal a novel mechanism of regulation in bacterial virulence that features a posttranslational modification and its dependence upon a co-factor specific for host cells.

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

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1572484

Report Number(s):: PNNL-SA-142888

Journal Information:: Nature, Vol. 572, Issue 7769

Country of Publication:: United States

Language:: English

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