Cryo-EM structures of an insecticidal Bt toxin reveal its mechanism of action on the membrane.

Cryo-EM structures of an insecticidal Bt toxin reveal its mechanism of action on the membrane.
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DOI:
10.1038/s41467-021-23146-4
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发表时间:
2021-05-14
影响因子:
16.6
通讯作者:
Thompson RF
Thompson RF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Byrne MJ;Iadanza MG;Perez MA;Maskell DP;George RM;Hesketh EL;Beales PA;Zack MD;Berry C;Thompson RF

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虫害是全球农作物损失的主要原因,每年估计造成4700亿美元的经济损失。已经引入了生物技术工具来控制这类昆虫,而不需要化学杀虫剂;例如,开发含有编码杀虫蛋白基因的转基因植物。苏云金芽孢杆菌Vip3(营养昆虫杀虫蛋白3)家族蛋白对鳞翅目昆虫具有毒害作用,在商业农业中具有广阔的应用前景。Vip3蛋白被认为通过形成气孔来发挥其杀虫活性,尽管到目前为止还没有机制描述这是如何在膜上发生的。在这里,我们介绍了Vip3家族毒素的冷冻-EM结构,包括非活性和活性两种形式,以及毒素-膜相互作用的结构和功能数据。综上所述,这些数据表明,激活的Vip3Bc1复合体能够以高效的方式插入膜,表明受体结合可能是Vip3特异性的驱动因素。苏云金芽孢杆菌的Vip3家族蛋白被认为是通过形成气孔来发挥杀虫活性的。作者提出了Vip3家族毒素的冷冻-EM结构,包括灭活和活化两种形式,并显示了活化的Vip3Bc1在膜上的成孔构象。
Insect pests are a major cause of crop losses worldwide, with an estimated economic cost of $470 billion annually. Biotechnological tools have been introduced to control such insects without the need for chemical pesticides; for instance, the development of transgenic plants harbouring genes encoding insecticidal proteins. The Vip3 (vegetative insecticidal protein 3) family proteins from Bacillus thuringiensis convey toxicity to species within the Lepidoptera, and have wide potential applications in commercial agriculture. Vip3 proteins are proposed to exert their insecticidal activity through pore formation, though to date there is no mechanistic description of how this occurs on the membrane. Here we present cryo-EM structures of a Vip3 family toxin in both inactive and activated forms in conjunction with structural and functional data on toxin–membrane interactions. Together these data demonstrate that activated Vip3Bc1 complex is able to insert into membranes in a highly efficient manner, indicating that receptor binding is the likely driver of Vip3 specificity. The Vip3 family proteins from Bacillus thuringiensis are thought to exert their insecticidal activity through pore formation. Here authors present cryo-EM structures of a Vip3 family toxin in both inactive and activated forms and show the activated Vip3Bc1 in its pore forming conformation on the membrane.
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