1. Microbiology and Infectious Disease
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Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes

  1. Shuxin Liu
  2. Luo Jiwei
  3. Xiangkai Zhen
  4. Jiazhang Qiu  Is a corresponding author
  5. Songying Ouyang  Is a corresponding author
  6. Zhao-Qing Luo  Is a corresponding author
  1. Jilin University, China
  2. Fujian Normal University, China
  3. Purdue University, United States
Research Article
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Cite this article as: eLife 2020;9:e58114 doi: 10.7554/eLife.58114

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.

Article and author information

Author details

  1. Shuxin Liu

    Department of Respiratory Medicine, Jilin University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Luo Jiwei

    School of Life Sciences, Fujian Normal University, Fuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiangkai Zhen

    The Key Laboratory of Innate Immune Biology of Fujian Province, College of Life Sciences, Fujian Normal University, Fuzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Jiazhang Qiu

    Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
    For correspondence
    qiujz@jlu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7723-5073
  5. Songying Ouyang

    College of Life Sciences, Fujian Normal University, Fuzhou, China
    For correspondence
    ouyangsy@fjnu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1120-1524
  6. Zhao-Qing Luo

    Biological Sciences, Purdue University, West Lafayette, United States
    For correspondence
    luoz@purdue.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8890-6621

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

  1. Wade Harper, Harvard Medical School, United States

Publication history

  1. Received: April 21, 2020
  2. Accepted: November 1, 2020
  3. Accepted Manuscript published: November 2, 2020 (version 1)
  4. Accepted Manuscript updated: November 3, 2020 (version 2)
  5. 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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