Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
- The University of Queensland, Australia
- 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
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Structure of the SNX5 PX domainPublicly available at the University of Queensland eSpace (UQ: 409277).
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Structure of the SNX5 PX domain in complex with chlamydial protein IncE in space group P212121Publicly available at the RCSB Protein Data Bank (accession no. 5TGI).
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Structure of the SNX5 PX domain in complex with chlamydial protein IncE in space group I2Publicly available at the RCSB Protein Data Bank (accession no. 5TGJ).
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Structure of the SNX5 PX domain in complex with chlamydial protein IncE in space group P32Publicly available at the RCSB Protein Data Bank (accession no. 5TGH).
Article and author information
Author details
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
© 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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Structural basis for the hijacking of endosomal sorting nexin proteins by Chlamydia trachomatis
eLife 6:e22311.
https://doi.org/10.7554/eLife.22311
Further reading
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