1. Biochemistry and Chemical Biology
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Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection

  1. Donghyuk Shin
  2. Anshu Bhattacharya
  3. Yi-Lin Cheng
  4. Marta Campos Alonso
  5. Ahmad Reza Mehdipour
  6. Gerbrand J van der Heden van Noort
  7. Huib Ovaa
  8. Gerhard Hummer
  9. Ivan Dikic  Is a corresponding author
  1. Institute of Biochemistry II, Germany
  2. Max Planck Institute of Biophysics, Germany
  3. Leiden University Medical Center, Netherlands
  4. Leiden University Medical Centre, Netherlands
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Cite this article as: eLife 2020;9:e58277 doi: 10.7554/eLife.58277

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.

Article and author information

Author details

  1. Donghyuk Shin

    Faculty of Medicine, Institute of Biochemistry II, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8272-6133
  2. Anshu Bhattacharya

    Faculty of Medicine, Institute of Biochemistry II, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7383-3594
  3. Yi-Lin Cheng

    Faculty of Medicine, Institute of Biochemistry II, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  4. Marta Campos Alonso

    Faculty of Medicine, Institute of Biochemistry II, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
  5. Ahmad Reza Mehdipour

    Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt, Germany
    Competing interests
    No competing interests declared.
  6. Gerbrand J van der Heden van Noort

    Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  7. Huib Ovaa

    Cell and Chemical Biology, Leiden University Medical Centre, Leiden, Netherlands
    Competing interests
    No competing interests declared.
  8. Gerhard Hummer

    Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7768-746X
  9. Ivan Dikic

    Faculty of Medicine, Institute of Biochemistry II, Frankfurt am Main, Germany
    For correspondence
    dikic@biochem2.uni-frankfurt.de
    Competing interests
    Ivan Dikic, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8156-9511

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

  1. Wade Harper, Harvard Medical School, United States

Publication history

  1. Received: April 26, 2020
  2. Accepted: November 12, 2020
  3. Accepted Manuscript published: November 13, 2020 (version 1)

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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