The bacterial deubiquitinase Ceg23 regulates the association of Lys-63-linked polyubiquitin molecules on the Legionella phagosome

33Citations
Citations of this article
24Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Legionella pneumophila is the causative agent of the lung malady Legionnaires' disease, it modulates host function to create a niche termed the Legionella-containing vacuole (LCV) that permits intracellular L. pneumophila replication. One important aspect of such modulation is the co-option of the host ubiquitin network with a panel of effector proteins. Here, using recombinantly expressed and purified proteins, analytic ultracentrifugation, structural analysis, and computational modeling, along with deubiquitinase (DUB), and bacterial infection assays, we found that the bacterial defective in organelle trafficking/intracellular multiplication effector Ceg23 is a member of the ovarian tumor (OTU) DUB family. We found that Ceg23 displays high specificity toward Lys-63-linked polyubiquitin chains and is localized on the LCV, where it removes ubiquitin moieties from proteins ubiquitinated by the Lys-63-chain type. Analysis of the crystal structure of a Ceg23 variant lacking two putative transmembrane domains at 2.80 Å resolution revealed that despite very limited homology to established members of theOTUfamily at the primary sequence level, Ceg23 harbors a catalytic motif resembling those associated with typical OTU-type DUBs. ceg23 deletion increased the association of Lys-63-linked polyubiquitin with the bacterial phagosome, indicating that Ceg23 regulates Lys-63-linked ubiquitin signaling on the LCV. In summary, our findings indicate that Ceg23 contributes to the regulation of the association of Lys-63 type polyubiquitin with the Legionella phagosome. Future identification of host substrates targeted by Ceg23 could clarify the roles of these polyubiquitin chains in the intracellular life cycle of L. pneumophila and Ceg23's role in bacterial virulence.

References Powered by Scopus

Processing of X-ray diffraction data collected in oscillation mode

39367Citations
N/AReaders
Get full text

Coot: Model-building tools for molecular graphics

26316Citations
N/AReaders
Get full text

PHENIX: A comprehensive Python-based system for macromolecular structure solution

19341Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Molecular mimicry: A paradigm of host-microbe coevolution illustrated by legionella

51Citations
N/AReaders
Get full text

Identification and characterization of diverse OTU deubiquitinases in bacteria

45Citations
N/AReaders
Get full text

Interplay between bacterial deubiquitinase and ubiquitin e3 ligase regulates ubiquitin dynamics on legionella phagosomes

36Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Ma, K., Zhen, X., Zhou, B., Gan, N., Cao, Y., Fan, C., … Qiu, J. (2020). The bacterial deubiquitinase Ceg23 regulates the association of Lys-63-linked polyubiquitin molecules on the Legionella phagosome. Journal of Biological Chemistry, 295(6), 1646–1657. https://doi.org/10.1074/jbc.RA119.011758

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 5

42%

Researcher 5

42%

Professor / Associate Prof. 2

17%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 8

57%

Immunology and Microbiology 4

29%

Agricultural and Biological Sciences 1

7%

Nursing and Health Professions 1

7%

Save time finding and organizing research with Mendeley

Sign up for free