细胞死亡途径中的动物和植物TIR域的NAD+分裂活动
Shane Horsefield1, Hayden Burdett1, Xiaoxiao Zhang2,3
1School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia.
概括
无菌的α和TIR动机含有1 (SARM1) 和植物免疫受体使用Toll/interleukin-1受体 (TIR) 域进行细胞死亡信号传递. 这些TIR域分裂尼古丁胺氨酸二核酸 (NAD+),这是动物和植物中保存的机制.
科学领域:
- 生物化学
- 细胞生物学
- 神经科学
背景情况:
- 含有1 (SARM1) 的无菌α和TIR基因通过耗尽尼古丁胺氨基二核酸 (NAD+) 来调解瓦莱尔退化.
- 植物核酸结合丰富的重复 (NLR) 免疫受体利用Toll/interleukin-1受体 (TIR) 域触发对病原体的细胞死亡.
研究的目的:
- 研究TIR域介导细胞死亡信号的酶活性和结构基础.
- 确定动物和植物细胞死亡途径中NAD+分裂的保存机制.
主要方法:
- 评估NAD+分裂活性的生物化学测试.
- 结构生物学技术,包括X射线晶体学,以确定蛋白质 - 连接体复合物.
- 生物物理方法来描述蛋白质的自我结合.
主要成果:
- SARM1和植物NLR TIR域表现出自关联依赖的NAD+裂变活性.
- SARM1无菌α基因组 (SAM) 域形成了对轴突退化和TIR域活性至关重要的八位体.
- 晶体结构显示了SARM1和植物NLR RUN1 TIR域中的NAD+的保存基质结合位.
结论:
- 通过TIR域的NAD+分裂是动物和植物细胞死亡信号所必需的保存酶活性.
- TIR域的结构和功能保存突出了跨王国的共享分子机制.
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