核酸诱导的NADase激活一个短 Sir2-关联的核细胞阿尔戈诺特系统的激活
Dapeng Sun1, Kaixiang Zhu2, Linyue Wang2
1Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
Cell reports
|June 26, 2024
概括
导向核酸的短 prokaryotic Argonaute (pAgo) 蛋白质仍然被人们理解得很少. 结构研究揭示了短pAgos如何结合核酸,引发构造变化,激活NADase活动以进行细胞防御.
科学领域:
- 结构生物学 结构生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 阿尔戈纳特 (Ago) 蛋白质对于核酸介导的抑制至关重要.
- 细胞和长 prokaryotic Ago 蛋白质 (pAgos) 有明确的功能.
- 短PAGOS的机制在很大程度上仍然是神秘的.
研究的目的:
- 为了阐明短 pAgo 函数的结构机制.
- 为了研究短pAgos与核酸和相关蛋白质的相互作用.
- 了解短 pAgo 复合体的酶活性.
主要方法:
- 确定了短 pAgo 复合体的两个冷电子显微镜结构.
- 分析了指导RNA-向DNA载荷的GsSir2/Ago四元复合物的结构.
- 检查了四元复合体的二维结构.
主要成果:
- 核酸结合会在短时间的pAgos中诱导显著的形状变化.
- Sir2域经历了乱或部分解离,表明NADase激活.
- 通过MID域进行加载的GsSir2/Ago复合物的二元化协同增强了NADase活动.
结论:
- 对短时间的pAgo介导核酸抑制的结构性见解.
- 证明了在核酸结合和复杂二元化过程中NADase激活的机制.
- 提供了对外国核酸的短期pAgo中介防御的结构基础.
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