8CQ2

Photorhabdus luminescens TcdA1 prepore-to-pore intermediate, C16S, C20S, C870S, T1279C mutant

8CQ2 の概要

• エントリーDOI: 10.2210/pdb8cq2/pdb
• EMDBエントリー: 16793
• 分子名称: TcdA1 (1 entity in total)
• 機能のキーワード: bacterial toxin, tc toxin, toxin
• 由来する生物種: Photorhabdus luminescens
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 1426648.13

構造登録者

Nganga, P.N.,Roderer, D.,Belyy, A.,Prumbaum, D.,Raunser, S. (登録日: 2023-03-03, 公開日: 2024-03-13, 最終更新日: 2025-01-22)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.6 Å)