非正规细菌DNA损伤反应途径的转录激活机制
Rajiv R Singh1, Amani Chinni2, Emily Cannistraci1
1Department of Biochemistry, 307 Research Dr., Box 3711, Duke University Medical Center, Durham, NC 27710, USA.
Research square
|August 13, 2025
概括
细菌DNA损伤反应涉及一种称为DriD的蛋白质,它与单链DNA (ssDNA) 结合并激活转录. 结构研究揭示了DriD如何运作.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 修复DNA损伤对于细菌的生存至关重要.
- 在*Caulobacter crescentus*中,非正规的DNA损伤反应是由WYL域转录因子DriD调解的.
- 在DNA受损时,DriD与单链DNA (ssDNA) 结合,以激活转录.
研究的目的:
- 阐明DriD介导的转录激活的机制.
- 确定DriD与RNAP全酶和促进体相互作用的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得结构.
- 确定了与RNAP全酶结合的DriD-ssDNA在三个不同的促进体中的结构.
主要成果:
- DriD拥有N端DNA结合域 (DNABD),通过3螺旋束 (3HB) 模块连接到WYL信号域.
- DriD的3HBs与RNAP的α-CTD和β域结合,将RNAP与非最佳促进体结合.
- 驱动DriD作为ssDNA触发的开关,3HBs在ssDNA结合时释放与DNABDs的自身抑制接触.
结论:
- 通过DriD激活转录的一个保存机制涉及它的3HBs与RNAP结合.
- DriD作为一个ssDNA激活的转录因子,利用其3HB模块作为触发器.
- 这种独特的转录激活机制很可能保留在同位体WYL激活蛋白中.
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