Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis

  1. Blessy Paul
  2. Hyun Sung Kim
  3. Markus C Kerr
  4. Wilhelmina M Huston
  5. Rohan D Teasdale  Is a corresponding author
  6. Brett M Collins  Is a corresponding author
  1. The University of Queensland, Australia
  2. University of Technology Sydney, Australia

Abstract

During infection chlamydial pathogens form an intracellular membrane-bound replicative niche termed the inclusion, which is enriched with bacterial transmembrane proteins called Incs. Incs bind and manipulate host cell proteins to promote inclusion expansion and provide camouflage against innate immune responses. Sorting nexin (SNX) proteins that normally function in endosomal membrane trafficking are a major class of inclusion-associated host proteins, and are recruited by IncE/CT116. Crystal structures of the SNX5 phox-homology (PX) domain in complex with IncE define the precise molecular basis for these interactions. The binding site is unique to SNX5 and related family members SNX6 and SNX32. Intriguingly the site is also conserved in SNX5 homologues throughout evolution, suggesting that IncE captures SNX5-related proteins by mimicking a native host protein interaction. These findings thus provide the first mechanistic insights both into how chlamydial Incs hijack host proteins, and how SNX5-related PX domains function as scaffolds in protein complex assembly.

Data availability

The following data sets were generated
    1. Collins B
    (2016) Structure of the SNX5 PX domain
    Publicly available at the University of Queensland eSpace (UQ: 409277).

Article and author information

Author details

  1. Blessy Paul

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Hyun Sung Kim

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Markus C Kerr

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Wilhelmina M Huston

    School of Life Sciences, University of Technology Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Rohan D Teasdale

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    For correspondence
    r.teasdale@imb.uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
  6. Brett M Collins

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    For correspondence
    b.collins@imb.uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6070-3774

Funding

National Health and Medical Research Council (APP1058734)

  • Brett M Collins

National Health and Medical Research Council (606788)

  • Rohan D Teasdale

National Health and Medical Research Council (APP1041929)

  • Brett M Collins

National Health and Medical Research Council (APP1061574)

  • Rohan D Teasdale

Australian Research Council (DP0985029)

  • Brett M Collins

Australian Research Council (DP150100364)

  • Brett M Collins

Australian Research Council (DE120102321)

  • Markus C Kerr

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

Reviewing Editor

  1. Suzanne R Pfeffer, Stanford University School of Medicine, United States

Publication history

  1. Received: October 12, 2016
  2. Accepted: February 19, 2017
  3. Accepted Manuscript published: February 22, 2017 (version 1)
  4. Version of Record published: March 13, 2017 (version 2)

Copyright

© 2017, Paul 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. Blessy Paul
  2. Hyun Sung Kim
  3. Markus C Kerr
  4. Wilhelmina M Huston
  5. Rohan D Teasdale
  6. Brett M Collins
(2017)
Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
eLife 6:e22311.
https://doi.org/10.7554/eLife.22311

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