Abstract
Legionella pneumophila extensively modulates the host ubiquitin network to create the Legionella-containing vacuole (LCV) for its replication. Many of its virulence factors function as ubiquitin ligases or deubiquitinases (DUBs). Here we identify Lem27 as a DUB that displays a preference for diubiquitin formed by K6, K11 or K48. Lem27 is associated with the LCV where it regulates Rab10 ubiquitination in concert with SidC and SdcA, two bacterial E3 ubiquitin ligases. Structural analysis of the complex formed by an active fragment of Lem27 and the substrate-based suicide inhibitor ubiquitin-propargylamide (PA) reveals that it harbors a fold resembling those in the OTU1 DUB subfamily with a Cys-His catalytic dyad and that it recognizes ubiquitin via extensive hydrogen bonding at six contact sites. Our results establish Lem27 as a deubiquitinase that functions to regulate protein ubiquitination on L. pneumophila phagosomes by counteracting the activity of bacterial ubiquitin E3 ligases.
Data availability
Diffraction data have been deposited in PDB under the accession code 7BU0.
Article and author information
Author details
Funding
National Natural Science Foundation of China (31770149)
- Jiazhang Qiu
National Natural Science Foundation of China (31970134)
- Jiazhang Qiu
National Natural Science Foundation of China (31770948)
- Songying Ouyang
National Natural Science Foundation of China (31570875)
- Songying Ouyang
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
Publication history
- Received: April 21, 2020
- Accepted: November 1, 2020
- Accepted Manuscript published: November 2, 2020 (version 1)
- Accepted Manuscript updated: November 3, 2020 (version 2)
- Version of Record published: November 16, 2020 (version 3)
Copyright
© 2020, Liu 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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