Journal
EMBO JOURNAL
Volume 36, Issue 23, Pages 3517-3531Publisher
WILEY
DOI: 10.15252/embj.201797515
Keywords
chaperone; EPEC; in vitro reconstitution; substrate switching; type III secretion
Categories
Funding
- KUL-Spa (Onderzoekstoelagen)
- KUL-Spa (Bijzonder Onderzoeksfonds)
- KUL-Spa (KU Leuven)
- RiMembR (Vlaanderen Onderzoeksprojecten)
- RiMembR [G0C6814N]
- RiMembR (FWO)
- T3RecS [G002516N]
- T3RecS (FWO)
- DIP-BiD [AKUL/15/40-G0H2116N]
- DIP-BiD (Hercules/FWO)
- FWO
- R&D Pilot project [Instruct, part of the European Strategy Forum on Research Infrastructures (ESFRI)]
- Wellcome Trust
- NIH [AI094623]
- [G0B4915N]
- MRC [MR/P028225/1] Funding Source: UKRI
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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.
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