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

Abstract
Data availability
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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).

http://espace.library.uq.edu.au/view/UQ:409277
1. Collins B
2. Paul B
(2017) Structure of the SNX5 PX domain in complex with chlamydial protein IncE in space group P212121
Publicly available at the RCSB Protein Data Bank (accession no. 5TGI).

http://www.rcsb.org/pdb/explore/explore.do?structureId=5TGI
1. Collins B
2. Paul B
(2017) Structure of the SNX5 PX domain in complex with chlamydial protein IncE in space group I2
Publicly available at the RCSB Protein Data Bank (accession no. 5TGJ).

http://www.rcsb.org/pdb/explore/explore.do?structureId=5TGJ
1. Collins B
2. Paul B
(2017) Structure of the SNX5 PX domain in complex with chlamydial protein IncE in space group P32
Publicly available at the RCSB Protein Data Bank (accession no. 5TGH).

http://www.rcsb.org/pdb/explore/explore.do?structureId=5TGH

Article and author information

Author details

Blessy Paul

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

Competing interests
The authors declare that no competing interests exist.
Hyun Sung Kim

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

Competing interests
The authors declare that no competing interests exist.
Markus C Kerr

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia

Competing interests
The authors declare that no competing interests exist.
Wilhelmina M Huston

School of Life Sciences, University of Technology Sydney, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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.

Copyright

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.