Abstract：
Destruxin A (DA) is a cyclo-hexadepsipeptidic insecticidal mycotoxin isolated from the entomopathogenic fungi, Metarhizium spp. However, its mode of action is unknown. In this study, we isolated 149 candidate DA-binding proteins by drug affinity response target stability, and determined the interactions of 80 canditates with DA in vitro by surface plasmon resonance. The affinity coefficients (KD) ranged from 24 to 469 μM. Binding proteins were functionally diverse and included cytoskeletal components and cell motility, protein transcription and translation pathways, ubiquitin dependent protein metabolic processes, nucleus pore entry and exit, and endoplasmic reticulum vesicle transport and etc. Electron microscopy revealed that DA damaged the cytoskeleton and multiple organelles, disrupted cell adhesion and motility, and led to cell death. DA appeared to have a multi-targeted approach to cellular structures and multiple life processes, leading to cell death. The results of this study could provide molecular evidence for the analysis of the insecticidal toxicology of DA and further improve the study of the pathogenic insect mechanism of Metarhizium.
摘要：
DestruxinA（DA）是从昆虫病原真菌中分离出的环六缩肽杀虫真菌毒素，绿僵菌属。然而,它的作用方式是未知的。在这项研究中,我们通过药物亲和反应靶标稳定性分离了149个候选DA结合蛋白，并通过表面等离子体共振测定了80种直烷酸与DA的体外相互作用。亲和力系数(KD)为24至469μM。结合蛋白功能多样，包括细胞骨架成分和细胞运动，蛋白质转录和翻译途径，泛素依赖性蛋白质代谢过程，核孔进出，内质网囊泡转运等。电镜显示DA损伤细胞骨架和多个细胞器,破坏细胞粘附和运动，导致细胞死亡.DA似乎对细胞结构和多个生命过程有多目标的方法，导致细胞死亡。本研究结果可为DA的杀虫毒理学分析提供分子依据,进一步完善对绿僵菌致病昆虫机理的研究。
