Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection
- Institute of Biochemistry II, Germany
- Max Planck Institute of Biophysics, Germany
- Leiden University Medical Center, Netherlands
- Leiden University Medical Centre, Netherlands
Abstract
Legionella pneumophila causes a severe pneumonia known as Legionnaires' disease. During the infection, Legionella injects more than 300 effector proteins into host cells. Among them are enzymes involved in altering the host-ubiquitination system. Here, we identified two Legionella OTU-like deubiquitinases (LOT; LotB (Lpg1621/Ceg23) and LotC (Lpg2529)). The crystal structure of the LotC catalytic core (LotC14-310) was determined at 2.4 Å. Unlike the classical OTU-family, the Legionella OTU-family shows an extended helical lobe between the Cys-loop and the variable loop, which defines them as a unique class of OTU-deubiquitinases. LotB has an additional ubiquitin-binding site (S1'), which enables the specific cleavage of Lys63-linked polyubiquitin chains. By contrast, LotC only contains the S1 site and cleaves different species of ubiquitin chains. MS analysis of LotB and LotC identified different categories of host-interacting proteins and substrates. Together, our results provide new structural insights into bacterial OTU deubiquitinases and indicate distinct roles in host-pathogen interactions.
Data availability
Diffraction data have been deposited in PDB under the accession code 6YK8.
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OTU-like deubiquitinase from Legionella- Lpg2529Protein data bank, 6YK8.
Article and author information
Author details
Anshu Bhattacharya
Funding
H2020 European Research Council (742720)
- Donghyuk Shin
- Anshu Bhattacharya
- Yi-Lin Cheng
- Marta Campos Alonso
Deutsche Forschungsgemeinschaft (ID 259139777)
- Ahmad Reza Mehdipour
- Gerhard Hummer
- Ivan Dikic
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wade Harper, Harvard Medical School, United States
Version history
- Received: April 26, 2020
- Accepted: November 12, 2020
- Accepted Manuscript published: November 13, 2020 (version 1)
- Version of Record published: November 26, 2020 (version 2)
Copyright
© 2020, Shin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection
eLife 9:e58277.
https://doi.org/10.7554/eLife.58277
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