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cGAS通过形成蛋白质-DNA梯子来感知长度和HMGB/TFAM结合的U转基因
Liudmila Andreeva1,2, Björn Hiller1,2, Dirk Kostrewa1,2
1Department of Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
Nature
|September 14, 2017
概括
循环GMP-AMP合成酶 (cGAS) 能够感知先天免疫的DNA长度. 像HMGB1和TFAM这样的DNA结合蛋白有助于cGAS检测较长的DNA,这对于识别病原体和线粒体DNA至关重要.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 细胞核DNA通过循环GMP-AMP合成酶 (cGAS) 触发先天免疫反应.
- cGAS感知DNA产生I型干扰素,但其DNA长度感知机制尚未完全理解.
- 内生DNA也可以激活cGAS,导致无菌炎症.
研究的目的:
- 为了研究cGAS的DNA长度依赖激活.
- 阐明cGAS二元化和DNA结合的机制.
- 识别调节cGASDNA传感的宿主因素.
主要方法:
- 在体外生化测试以测量cGAS激活.
- 基于细胞的测试使用人类细胞来评估cGAS活性.
- 对cGAS-DNA复合体的形成和结构的分析.
主要成果:
- cGAS激活高度依赖于DNA长度,较长的DNA是一种更强的激活剂.
- cGAS二极管与DNA形成类似梯子的网络,使得DNA长度的协同感知.
- 通过诱导DNA曲,细菌 (HU),线粒体 (TFAM) 和HMGB1蛋白显著增强长DNA的cGAS感应.
结论:
- 一个核合作机制解释了病原体和线粒体DNA的敏感cGAS检测.
- HMGB1和TFAM作为促进cGAS激活的DNA结构的主体因素.
- cGAS优先结合曲的DNA和不完整的核状结构.
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