一个包含转录调节器的WYL域DriD的Allosteric激活机制
Emily Cannistraci1, Bindu Y Srinivasu2, Jose Chavez Orozco1
1Department of Biochemistry, 307 Research Dr., Box 3711, Duke University Medical Center, Durham, NC, 27710, USA.
Communications biology
|April 29, 2025
概括
具有WYL域的转录因子调节细菌过程. 研究人员发现了DriD如何感知单链DNA (ssDNA) 来激活DNA结合和修复途径,揭示了一个新的全性机制.
科学领域:
- 细菌转录调节 细菌转录调节
- DNA修复的分子机制
- 蛋白质全ostery是蛋白质的全ostery.
背景情况:
- 含有转录因子的WYL域对细菌生理学至关重要.
- 这些因素的精确传感机制和全激活在很大程度上是未知的.
- 了解这些调节剂至关重要,特别是在致病性细菌中.
研究的目的:
- 为了阐明DriD的全性激活机制,DriD是Caulobacter crescentus的一种转录调节剂.
- 了解DriD如何感知单链DNA (ssDNA) 来启动DNA损伤反应.
- 提供一个模型,用于激活同位基 WYL 激活器.
主要方法:
- 进行X射线晶体学以确定结构变化.
- 生物化学测试以评估蛋白质相互作用和DNA结合.
- -交换质谱 (HDX-MS) 用于绘制形状动态图.
主要成果:
- 在DNA受损时,DriD通过其WYL域直接感知ssDNA.
- ssDNA结合缓解了DNA结合域 (DNABD) 和三螺旋捆 (3HB) 域之间的自身抑制相互作用.
- 这种结构重组使得DriD的目标DNA结合并激活非正规DNA损伤途径.
结论:
- 这项研究揭示了ssDNA对DriD激活的新型全性机制.
- 这种机制涉及在 cue 感知时释放分子内抑制.
- 这些发现提供了对WYL域调节者的更广泛家族的见解,以及它们在细菌生存和病原发生中的作用.
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