Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester, LE1 7HB, UK.
Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY, UK.
Nat Commun. 2019 Jun 14;10(1):2641. doi: 10.1038/s41467-019-10645-8.
Epsilon toxin (Etx), a potent pore forming toxin (PFT) produced by Clostridium perfringens, is responsible for the pathogenesis of enterotoxaemia of ruminants and has been suggested to play a role in multiple sclerosis in humans. Etx is a member of the aerolysin family of β-PFTs (aβ-PFTs). While the Etx soluble monomer structure was solved in 2004, Etx pore structure has remained elusive due to the difficulty of isolating the pore complex. Here we show the cryo-electron microscopy structure of Etx pore assembled on the membrane of susceptible cells. The pore structure explains important mutant phenotypes and suggests that the double β-barrel, a common feature of the aβ-PFTs, may be an important structural element in driving efficient pore formation. These insights provide the framework for the development of novel therapeutics to prevent human and animal infections, and are relevant for nano-biotechnology applications.
epsilon 毒素（Etx）是产气荚膜梭菌产生的一种强效的孔形成毒素（PFT），它是反刍动物肠毒血症的致病因子，并被认为在人类多发性硬化症中起作用。Etx 是 aerolysin 家族的β-PFTs（aβ-PFTs）的成员。虽然 Etx 可溶性单体结构在 2004 年被解析，但由于难以分离孔复合物，Etx 孔结构仍然难以捉摸。在这里，我们展示了在易感细胞的膜上组装的 Etx 孔的冷冻电子显微镜结构。该孔结构解释了重要的突变表型，并表明双 β-桶，aβ-PFTs 的共同特征，可能是驱动有效孔形成的重要结构元素。这些见解为开发预防人类和动物感染的新型治疗方法提供了框架，并且与纳米生物技术应用相关。
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