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.
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Shuxin Liu
Department of Respiratory Medicine, Jilin University, Changchun, China
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The authors declare that no competing interests exist.
Luo Jiwei
School of Life Sciences, Fujian Normal University, Fuzhou, China
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The authors declare that no competing interests exist.
Xiangkai Zhen
The Key Laboratory of Innate Immune Biology of Fujian Province, College of Life Sciences, Fujian Normal University, Fuzhou, China
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The authors declare that no competing interests exist.
Jiazhang Qiu
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
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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