植物AtLSD1蛋白调控细胞程序性死亡的分子机制研究

Programmed cell death has important biological significance for the normal growth and development of plants and its pathological processes, AtLSD1 (lesion simulating disease 1) is a key negative regulatory factor for programmed cell death in Arabidopsis thaliana. By sensing intracellular reactive oxygen species signals, AtLSD1 inhibits the positive regulation of AtMC1 (metacaspase 1) on cell death and regulates the activity of transcription factor AtbZIP10 (basic leucine zipper 10). The structures of AtLSD1, AtMC1, AtbZIP10 and their homologous proteins have not been reported. We have obtained the crystals of AtLSD1 with a diffraction resolution up to 2.9 Å. This project will continue to resolve the structure of AtLSD1 and its complex structures with AtMC1 N-terminal and AtbZIP10 C-terminal fragments using means of structural biology and biochemistry. Based on these structures, on the level of biochemistry and cell biology, we will then design functional experiments to elucidate the molecular mechanism of how AtLSD1 regulates the interaction proteins by sensing intracellular redox state. The results will guide and promote the mechanism research of programmed cell death of plants in response to adversity stresses.

细胞程序性死亡对于植物的正常生长发育及病理过程具有十分重要的生物学意义，AtLSD1（lesion simulating disease1）是拟南芥中细胞程序性死亡的一个关键负调控因子。AtLSD1通过感知细胞内的活性氧信号，抑制AtMC1（metacaspase1）的促细胞死亡作用和调控转录因子AtbZIP10（basic leucine zipper10）的活性。AtLSD1、AtMC1、AtbZIP10及其同源蛋白的结构尚未被报道。我们已获得AtLSD1晶体，衍射分辨率达2.9Å。本项目将继续通过结构生物学和生物化学的方法，解析AtLSD1及其与AtMC1 N端、AtbZIP10 C端片段的复合物结构。基于结构信息设计功能实验，在生化和细胞水平阐明AtLSD1如何通过感知细胞内氧化还原状态，来调控互作蛋白的分子机理。所得结论将指导并推进植物响应逆境胁迫而发生程序性细胞死亡机制的研究。

细胞程序性死亡对于植物的正常生长发育及病理过程具有十分重要的生物学意义，AtLSD1（lesion simulating disease1）是拟南芥中细胞程序性死亡的一个关键负调控因子。AtLSD1通过感知细胞内的活性氧信号，抑制AtMC1（metacaspase1）的促细胞死亡作用和调控转录因子AtbZIP10（basic leucine zipper 10）的活性。AtLSD1、AtMC1、AtbZIP10及其同源蛋白的结构尚未被报道。我们已收集多套AtLSD1晶体衍射数据，最高衍射分辨率达2.7Å；同时也生长出用镉离子替换AtLSD1锌指结构锌离子的晶体，测试分辨率在3 Å左右。体外组装出性质较好的AtLSD1-AtMC1 N端融合蛋白与AtLSD1的复合物。本项目将继续通过结构生物学和生物化学的方法，解析AtLSD1及其与AtMC1 N端、AtbZIP10 C端片段的复合物结构。基于结构信息设计功能实验，在生化和细胞水平阐明AtLSD1如何通过感知细胞内氧化还原状态，来调控互作蛋白的分子机理。所得结论将指导并推进植物响应逆境胁迫而发生程序性细胞死亡机制的研究。