Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction
- University of California, San Francisco, United States
Abstract
Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete a unique class of proteins, Incs, which insert into the inclusion membrane and modulate the host-bacterium interface. We previously reported that IncE binds specifically to the Sorting Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking. Here, we present the crystal structure of the SNX5-PX:IncE complex, showing IncE bound to a unique and highly conserved hydrophobic groove on SNX5. Mutagenesis of the SNX5-PX:IncE binding surface disrupts a previously unsuspected interaction between SNX5 and the cation-independent mannose-6-phosphate receptor (CI-MPR). Addition of IncE peptide inhibits the interaction of CI-MPR with SNX5. Finally, C. trachomatis infection interferes with the SNX5:CI-MPR interaction, suggesting that IncE and CI-MPR are dependent on the same binding surface on SNX5. Our results provide new insights into retromer assembly and underscore the power of using pathogens to discover disease-related cell biology.
Article and author information
Author details
Funding
National Institutes of Health (K08AI091656)
- Oren S Rosenberg
National Institutes of Health (AI073770)
- Joanne N Engel
National Institutes of Health (AI105561)
- Joanne N Engel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Suzanne R Pfeffer, Stanford University School of Medicine, United States
Version history
- Received: October 26, 2016
- Accepted: February 26, 2017
- Accepted Manuscript published: March 2, 2017 (version 1)
- Version of Record published: March 23, 2017 (version 2)
Copyright
© 2017, Elwell 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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Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction
eLife 6:e22709.
https://doi.org/10.7554/eLife.22709
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