Abstract

Bacterial type IV secretion systems (T4SSs) are molecular machines that can mediate interbacterial DNA transfer through conjugation and delivery of effector molecules into host cells. The Helicobacter pylori Cag T4SS translocates CagA, a bacterial oncoprotein, into gastric cells, contributing to gastric cancer pathogenesis. We report the structure of a membrane-spanning Cag T4SS complex, which contains three sub-complexes: a 14-fold symmetric outer membrane core complex (OMCC), 17-fold symmetric periplasmic ring complex (PRC), and stalk domain. Features that differ markedly from those of prototypical T4SSs include an expanded OMCC and unexpected symmetry mismatch between the OMCC and PRC. This structure is one of the largest bacterial secretion system complexes ever reported and illustrates the remarkable structural diversity that exists among bacterial T4SSs.

Data availability

The cryo-EM volumes have been deposited in the Electron Microscopy Data Bank under accession codes EMD-20023 (T4SS C1 reconstruction), EMD-20020 (Focused OMCC Reconstruction), EMD-20022 (OMCC Asymmetric Reconstruction), EMD-20021 (Focused PRC Reconstruction). Map coordinates have been deposited in the Protein Data Bank under accession numbers 6OEE (CagT), 6OEG (CagX), and 6ODI (CagY), 6OEF (O-layer), 6OEH (I-Layer), and 6ODJ (PRC).

The following data sets were generated

Article and author information

Author details

  1. Jeong Min Chung

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4285-8764
  2. Michael J Sheedlo

    Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Anne M Campbell

    Department of Medicine, Vanderbilt University School of Medicine, Nasvhille, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Neha Sawhney

    Department of Medicine, Vanderbilt University School of Medicine, Nasvhille, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4943-1018
  5. Arwen E Frick-Cheng

    Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Dana Borden Lacy

    Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nasvhille, United States
    For correspondence
    borden.lacy@vumc.org
    Competing interests
    The authors declare that no competing interests exist.
  7. Timothy L Cover

    Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, United States
    For correspondence
    timothy.l.cover@vumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8503-002X
  8. Melanie D Ohi

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    For correspondence
    mohi@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1750-4793

Funding

National Institute of Allergy and Infectious Diseases (AI118932)

  • Timothy L Cover
  • Melanie D Ohi

National Cancer Institute (CA116087)

  • Timothy L Cover

Department of Veterans' Affairs (1I01BX004447)

  • Timothy L Cover

National Institute of General Medical Sciences (GM103310)

  • Melanie D Ohi

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

Copyright

© 2019, Chung 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. Jeong Min Chung
  2. Michael J Sheedlo
  3. Anne M Campbell
  4. Neha Sawhney
  5. Arwen E Frick-Cheng
  6. Dana Borden Lacy
  7. Timothy L Cover
  8. Melanie D Ohi
(2019)
Structure of the Helicobacter pylori Cag Type IV secretion system
eLife 8:e47644.
https://doi.org/10.7554/eLife.47644

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https://doi.org/10.7554/eLife.47644