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聚胺代谢控制B-to-ZDNA转换,以调节DNA传感器cGAS活动

Chunyuan Zhao¹, Yunjin Ma², Minghui Zhang²

¹Department of Pathogenic Biology, Key Laboratory of Infection and Immunity of Shandong Province, and Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Cell Biology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

|October 17, 2023

概括

精氨酸和精氨酸等多氨酸通过诱导Z-DNA来降低循环氨酸单酸 (GMP) -AMP (cGAMP) 合成酶 (cGAS) 的活性. SAT1酶对此进行调节,影响天生的免疫力和病毒复制.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
生物化学生化学

背景情况:

循环氨酸单酸 (GMP) -AMP (cGAMP) 合成酶 (cGAS) 是细胞质双链DNA (dsDNA) 的关键传感器,启动先天免疫反应.
cGAS激活导致cGAMP的产生,该蛋白通过干扰素基因刺激器 (STING) 途径发出信号.

研究的目的:

研究内源多氨酸,精氨酸和精氨酸在调节cGAS活性和天生的免疫力中的作用.
阐明聚氨影响cGAS功能的分子机制.

主要方法:

评估精氨酸和精氨酸对cGAS-dsDNA结合亲和力的影响.
分析聚氨酸对DNA构成的影响 (B-DNA与Z-DNA对比).
评估Spermidine/spermine N1-乙转移酶1 (SAT1) 在聚胺代谢和cGAS激活中的作用.
研究SAT1缺乏对简单疹病毒1 (HSV-1) 在体内复制的影响.

主要成果:

发现精子和精子胺可以减弱cGAS活性和下游天生的免疫反应.
多氨酸诱导了dSDNA的形状变化,从B型变为Z型,减少了cGAS结合.
参与聚胺代谢的SAT1,通过防止Z-DNA积累,增强了cGAS激活.
在体内,SAT1缺乏导致HSV-1复制的增加.

结论:

内源多氨酸精氨酸和精氨酸调节cGAS介导的先天免疫力,通过诱导dSDNA采用Z形形态.
通过SAT1介导的聚胺代谢在调节cGAS活动和控制病毒感染方面发挥着至关重要的作用.

关键词:

这就是B-DNA.这就是Z-DNA.cGAS 是一个气体.这是先天免疫力.聚胺的新陈代谢精子中的精子.精子精子精子精子第一种类型的IFN.

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