8CQ0

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

Summary for 8CQ0

• Entry DOI: 10.2210/pdb8cq0/pdb
• EMDB information: 16792
• Descriptor: TcdA1 (1 entity in total)
• Functional Keywords: bacterial toxin, tc toxin, toxin
• Biological source: Photorhabdus luminescens
• Total number of polymer chains: 5
• Total formula weight: 1427449.22

Authors

Nganga, P.N.,Roderer, D.,Belyy, A.,Prumbaum, D.,Raunser, S. (deposition date: 2023-03-03, release date: 2024-03-13, Last modification date: 2025-01-22)

Primary citation

Ng'ang'a, P.N.,Folz, J.,Kucher, S.,Roderer, D.,Xu, Y.,Sitsel, O.,Belyy, A.,Prumbaum, D.,Kuhnemuth, R.,Assafa, T.E.,Dong, M.,Seidel, C.A.M.,Bordignon, E.,Raunser, S.
Multistate kinetics of the syringe-like injection mechanism of Tc toxins.
Sci Adv, 11:eadr2019-eadr2019, 2025

PubMed 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.

PubMed: 39752508
DOI: 10.1126/sciadv.adr2019

Experimental method

ELECTRON MICROSCOPY (3.2 Å)