EMD-16792

Single-particle
3.2 Å
EMD-16792 Deposition: 03/03/2023
Map released: 13/03/2024
Last modified: 22/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-16792

Photorhabdus luminescens TcdA1 prepore-to-pore intermediate, K567W K2008W mutant

EMD-16792

Single-particle
3.2 Å
EMD-16792 Deposition: 03/03/2023
Map released: 13/03/2024
Last modified: 22/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Photorhabdus luminescens
Sample: TcdA1
Fitted models: 8cq0 (Avg. Q-score: 0.466)

Deposition Authors: Nganga PN , Roderer D , Belyy A , Prumbaum D , Raunser S
Multistate kinetics of the syringe-like injection mechanism of Tc toxins.
Ng'ang'a PN , Folz J , Kucher S, Roderer D , Xu Y , Sitsel O , Belyy A , Prumbaum D , Kuhnemuth R, Assafa TE , Dong M , Seidel CAM , Bordignon E , Raunser S
(2025) Sci Adv , 11 , eadr2019 - eadr2019
PUBMED: 39752508
DOI: doi:10.1126/sciadv.adr2019
ISSN: 2375-2548
Abstract:
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.