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TitleMultistate kinetics of the syringe-like injection mechanism of Tc toxins.
Journal, issue, pagesSci Adv, Vol. 11, Issue 1, Page eadr2019, Year 2025
Publish dateJan 3, 2025
AuthorsPeter Njenga Ng'ang'a / Julian Folz / Svetlana Kucher / Daniel Roderer / Ying Xu / Oleg Sitsel / Alexander Belyy / Daniel Prumbaum / Ralf Kühnemuth / Tufa E Assafa / Min Dong / Claus A M Seidel / Enrica Bordignon / Stefan Raunser /
PubMed AbstractTc toxins are pore-forming virulence factors of many pathogenic bacteria. Following pH-induced conformational changes, they perforate the target membrane like a syringe to translocate toxic enzymes ...Tc toxins are pore-forming virulence factors of many pathogenic bacteria. Following pH-induced conformational changes, they perforate the target membrane like a syringe to translocate toxic enzymes into a cell. Although this complex transformation has been structurally well studied, the reaction pathway and the resulting temporal evolution have remained elusive. We used an integrated biophysical approach to monitor prepore-to-pore transition and found a reaction time of ~30 hours for a complete transition. We show two asynchronous general steps of the process, shell opening and channel ejection, with the overall reaction pathway being a slow multistep process involving three intermediates. Liposomes, an increasingly high pH, or receptors facilitate shell opening, which is directly correlated with an increased rate of the prepore-to-pore transition. Channel ejection is a near-instantaneous process which occurs with a transition time of <60 milliseconds. Understanding the mechanism of action of Tc toxins and unveiling modulators of the kinetics are key steps toward their application as biomedical devices or biopesticides.
External linksSci Adv / PubMed:39752508 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.6 Å
Structure data

16791

8cpz

EMDB-16791, PDB-8cpz:
Photorhabdus luminescens TcdA1 prepore-to-pore intermediate, K1179W mutant
Method: EM (single particle) / Resolution: 2.9 Å

16792

8cq0

EMDB-16792, PDB-8cq0:
Photorhabdus luminescens TcdA1 prepore-to-pore intermediate, K567W K2008W mutant
Method: EM (single particle) / Resolution: 3.2 Å

16793

8cq2

EMDB-16793, PDB-8cq2:
Photorhabdus luminescens TcdA1 prepore-to-pore intermediate, C16S, C20S, C870S, T1279C mutant
Method: EM (single particle) / Resolution: 3.6 Å

Source
  • photorhabdus luminescens (bacteria)
KeywordsTOXIN / Bacterial toxin / Tc toxin

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