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Elife. 2017 Mar 2;6. pii: e22709. doi: 10.7554/eLife.22709.

Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction.

Author information

1
Department of Medicine, University of California, San Francisco, San Francisco, United States.
2
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
3
QB3, California Institute for Quantitative Biosciences, San Francisco, United States.
4
Gladstone Institutes, San Francisco, United States.
5
Department of Microbiology and Immunology, University of California, San Francisco, 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.

KEYWORDS:

Chlamydia trachomatis; bacterial pathogenesis; biophysics; human; infectious disease; mannose-6-phosphate receptor; microbiology; retromer; sorting nexin; structural biology

PMID:
28252385
PMCID:
PMC5364026
DOI:
10.7554/eLife.22709
[Indexed for MEDLINE]
Free PMC Article

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