Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC

  1. David Jon Wasilko
  2. Qingqiu Huang
  3. Yuxin Mao  Is a corresponding author
  1. Cornell University, United States

Abstract

The causative agent of Legionnaires' disease, Legionella pneumophila, delivers more than 330 virulent effectors to its host to establish an intracellular membrane-bound organelle called the Legionella containing vacuole. Among the army of Legionella effectors, SidC and its paralog SdcA have been identified as novel bacterial ubiquitin (Ub) E3 ligases. To gain insight into the molecular mechanism of SidC/SdcA as Ub ligases, we determined the crystal structures of a binary complex of the N-terminal catalytic SNL domain of SdcA with its cognate E2 UbcH5C and a ternary complex consisting of the SNL domain of SidC with the Ub-linked E2 UbcH7. These two structures reveal the molecular determinants governing the Ub transfer cascade catalyzed by SidC. Together, our data support a common mechanism in the Ub transfer cascade in which the donor Ub is immobilized with its C-terminal tail locked in an extended conformation, priming the donor Ub for catalysis.

Data availability

Atomic coordinates and structure factors for the reported structures have been deposited into the Protein Data Bank under the accession codes 6CP0 (SdcA-UbcH5C), 6CP2 (SidC-UbcH7~Ub)

The following data sets were generated
    1. Wasilko DJ
    2. Huang Q
    3. Mao Y
    (2018) structure for SdcA-UbcH5C
    Publicly available at the RCSB Protein Data Bank (accession no. 6CP0).
    1. Wasilko DJ
    2. Huang Q
    3. Mao Y
    (2018) structure for SidC-UbcH7~Ub
    Publicly available at the RCSB Protein Data Bank (accession no. 6CP2).

Article and author information

Author details

  1. David Jon Wasilko

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Qingqiu Huang

    MacCHESS, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuxin Mao

    Molecualr Biology and Genetics/Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States
    For correspondence
    ym253@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5064-1397

Funding

National Institute of General Medical Sciences (5R01GM116964)

  • Yuxin Mao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Cynthia Wolberger, Johns Hopkins University, United States

Version history

  1. Received: February 23, 2018
  2. Accepted: July 16, 2018
  3. Accepted Manuscript published: July 17, 2018 (version 1)
  4. Version of Record published: July 27, 2018 (version 2)

Copyright

© 2018, Wasilko 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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  1. David Jon Wasilko
  2. Qingqiu Huang
  3. Yuxin Mao
(2018)
Insights into the ubiquitin transfer cascade catalyzed by the Legionella effector SidC
eLife 7:e36154.
https://doi.org/10.7554/eLife.36154

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