1. Structural Biology and Molecular Biophysics

The structure of the endogenous ESX-3 secretion system

  1. Nicole Poweleit
  2. Nadine Czudnochowski
  3. Rachel Nakagawa
  4. Donovan Trinidad
  5. Kenan C Murphy
  6. Christopher M Sassetti
  7. Oren S Rosenberg  Is a corresponding author
  1. University of California, San Francisco, United States
  2. University of Massachusetts Medical School, United States
https://doi.org/10.7554/eLife.52983
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  1. Nicole Poweleit
  2. Nadine Czudnochowski
  3. Rachel Nakagawa
  4. Donovan Trinidad
  5. Kenan C Murphy
  6. Christopher M Sassetti
  7. Oren S Rosenberg
(2019)
The structure of the endogenous ESX-3 secretion system
eLife 8:e52983.
https://doi.org/10.7554/eLife.52983
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Abstract

The ESX (or Type VII) secretion systems are protein export systems in mycobacteria and many Gram-positive bacteria that mediate a broad range of functions including virulence, conjugation, and metabolic regulation. These systems translocate folded dimers of WXG100-superfamily protein substrates across the cytoplasmic membrane. We report the cryo-electron microscopy structure of an ESX-3 system, purified using an epitope tag inserted with recombineering into the chromosome of the model organism Mycobacterium smegmatis. The structure reveals a stacked architecture that extends above and below the inner membrane of the bacterium. The ESX-3 protomer complex is assembled from a single copy of the EccB3, EccC3, and EccE3 and two copies of the EccD3 protein. In the structure, the protomers form a stable dimer that is consistent with assembly into a larger oligomer. The ESX-3 structure provides a framework for further study of these important bacterial transporters.

Data availability

The map files have been deposited at the EMDB with code 20820. The entry is online at https://www.ebi.ac.uk/pdbe/entry/emdb/EMD-20820.The model has been deposited at the PDB with the code 6UMM. It is online at http://www.rcsb.org/structure/6UMM

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Author details

  1. Nicole Poweleit

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Nadine Czudnochowski

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Rachel Nakagawa

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Donovan Trinidad

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Kenan C Murphy

    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Christopher M Sassetti

    Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Oren S Rosenberg

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    For correspondence
    oren.rosenberg@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5736-4388

Funding

National Institutes of Health (1RO1AI128214)

  • Oren S Rosenberg

National Institutes of Health (1U19AI135990-01)

  • Oren S Rosenberg

National Institutes of Health (P01AI095208)

  • Oren S Rosenberg

National Institutes of Health (5T32AI060537)

  • Nicole Poweleit

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

Reviewing Editor

  1. Edward H Egelman, University of Virginia, United States

Version history

  1. Received: October 23, 2019
  2. Accepted: December 30, 2019
  3. Accepted Manuscript published: December 30, 2019 (version 1)
  4. Version of Record published: January 28, 2020 (version 2)

Copyright

© 2019, Poweleit 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. Nicole Poweleit
  2. Nadine Czudnochowski
  3. Rachel Nakagawa
  4. Donovan Trinidad
  5. Kenan C Murphy
  6. Christopher M Sassetti
  7. Oren S Rosenberg
(2019)
The structure of the endogenous ESX-3 secretion system
eLife 8:e52983.
https://doi.org/10.7554/eLife.52983

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