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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.

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


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.


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

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