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

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

  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.

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.

Metrics

  • 1,724
    views
  • 270
    downloads
  • 41
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shuxin Liu
  2. Luo Jiwei
  3. Xiangkai Zhen
  4. Jiazhang Qiu
  5. Songying Ouyang
  6. Zhao-Qing Luo
(2020)
Interplay between bacterial deubiquitinase and ubiquitin E3 ligase regulates ubiquitin dynamics on Legionella phagosomes
eLife 9:e58114.
https://doi.org/10.7554/eLife.58114

Share this article

https://doi.org/10.7554/eLife.58114

Further reading

    1. Computational and Systems Biology
    2. Neuroscience
    Pedro J Gonçalves, Jan-Matthis Lueckmann ... Jakob H Macke
    Research Article Updated

    Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.

    1. Ecology
    2. Microbiology and Infectious Disease
    Tom Clegg, Samraat Pawar
    Research Article Updated

    Predicting how species diversity changes along environmental gradients is an enduring problem in ecology. In microbes, current theories tend to invoke energy availability and enzyme kinetics as the main drivers of temperature-richness relationships. Here, we derive a general empirically-grounded theory that can explain this phenomenon by linking microbial species richness in competitive communities to variation in the temperature-dependence of their interaction and growth rates. Specifically, the shape of the microbial community temperature-richness relationship depends on how rapidly the strength of effective competition between species pairs changes with temperature relative to the variance of their growth rates. Furthermore, it predicts that a thermal specialist-generalist tradeoff in growth rates alters coexistence by shifting this balance, causing richness to peak at relatively higher temperatures. Finally, we show that the observed patterns of variation in thermal performance curves of metabolic traits across extant bacterial taxa is indeed sufficient to generate the variety of community-level temperature-richness responses observed in the real world. Our results provide a new and general mechanism that can help explain temperature-diversity gradients in microbial communities, and provide a quantitative framework for interlinking variation in the thermal physiology of microbial species to their community-level diversity.