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

• Main Authors: Cherilyn A Elwell, Nadine Czudnochowski, John von Dollen, Jeffrey R Johnson, Rachel Nakagawa, Kathleen Mirrashidi, Nevan J Krogan, Joanne N Engel, Oren S Rosenberg
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-03-01
• Series: eLife
• Subjects: Chlamydia trachomatis; retromer; sorting nexin; bacterial pathogenesis; mannose-6-phosphate receptor
• Online Access: https://elifesciences.org/articles/22709

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.