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

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

Blog Article

Chlamydia trachomatis is an obligate COMMODES 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 Shorts 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.