3 years ago

Hierarchical protein targeting and secretion is controlled by an affinity switch in the type III secretion system of enteropathogenic Escherichia coli

Hierarchical protein targeting and secretion is controlled by an affinity switch in the type III secretion system of enteropathogenic Escherichia coli
Konstantinos C Tsolis, Valerie F Crepin, Anastassios Economou, Spyridoula Karamanou, Gad Frankel, Josep Rayo, Maria S Loos, Athina G Portaliou, Charalampos G Kalodimos, Alexandra Tsirigotaki, Vassileia Balabanidou
Type III secretion (T3S), a protein export pathway common to Gram-negative pathogens, comprises a trans-envelope syringe, the injectisome, with a cytoplasm-facing translocase channel. Exported substrates are chaperone-delivered to the translocase, EscV in enteropathogenic Escherichia coli, and cross it in strict hierarchical manner, for example, first “translocators”, then “effectors”. We dissected T3S substrate targeting and hierarchical switching by reconstituting them in vitro using inverted inner membrane vesicles. EscV recruits and conformationally activates the tightly membrane-associated pseudo-effector SepL and its chaperone SepD. This renders SepL a high-affinity receptor for translocator/chaperone pairs, recognizing specific chaperone signals. In a second, SepD-coupled step, translocators docked on SepL become secreted. During translocator secretion, SepL/SepD suppress effector/chaperone binding to EscV and prevent premature effector secretion. Disengagement of the SepL/SepD switch directs EscV to dedicated effector export. These findings advance molecular understanding of T3S and reveal a novel mechanism for hierarchical trafficking regulation in protein secretion channels. In vitro reconstitution shows that the Escherichia coli gatekeeper SepL and chaperone SepD prevent premature effector protein secretion by regulating their affinity to the export machinery.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.15252/embj.201797515

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