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The Chlamydia effector IncE employs two short linear motifs to reprogram host vesicle trafficking

Pha, K.; Mirrashidi, K.; Sherry, J.; Tran, C. J.; Herrera, C. M.; McMahon, E.; Elwell, C.; Engel, J.

2024-04-24 microbiology
10.1101/2024.04.23.590830 bioRxiv
Show abstract

Chlamydia trachomatis, a leading cause of bacteria sexually transmitted infections, creates a specialized intracellular replicative niche by translocation and insertion of a diverse array of effectors (Incs) into the inclusion membrane. Here, we characterize IncE, a multi-functional Inc that encodes two non-overlapping short linear motifs (SLiMs) within its short cytosolic C-terminus. The proximal SLiM mimics an R-SNARE motif to recruit syntaxin (STX) 7 and 12-containing vesicles to the inclusion. The distal SLiM mimics the Sorting Nexin (SNX) 5 and 6 cargo binding site to recruit SNX6-containing vesicles to the inclusion. By simultaneously binding to two distinct vesicle classes, IncE reprograms host cell trafficking to promote the formation of a class of hybrid vesicles at the inclusion that are required for C. trachomatis intracellular development. Our work suggests that Incs may have evolved SLiMs to facilitate rapid evolution in a limited protein space to disrupt host cell processes.

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