由OmpR/PhoB家族反应调节器PmrA的转录激活的结构基础
Yuan-Chao Lou1, Hsuan-Yu Huang2, Hsin-Hong Yeh3
1Biomedical Translation Research Center, Academia Sinica, Taipei 11529, Taiwan.
Nucleic acids research
|September 4, 2023
概括
一种细菌调节剂PmrA通过与特定的DNA序列结合来激活多素耐药基因. 一个冷EM结构揭示了PmrA如何与RNA聚合酶相互作用,影响转录和细菌防御机制.
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:
- PmrA是一种反应调节剂,控制细菌中的多素耐药性.
- 它识别了一个特定的DNA序列 (pmra-box),取代了正规的-35促销元件.
- 了解PmrA依赖转录激活复合体 (TAC) 对细菌耐药机制至关重要.
研究的目的:
- 为了确定PmrA依赖转录激活的结构基础.
- 阐明PmrA,RNA聚合酶和促进DNA之间的相互作用.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得TAC的结构.
- 进行了体内测试,以验证观察到的相互作用的功能意义.
主要成果:
- 冷-EM结构揭示了一个动态的TAC构造与PmrA二聚体和RNA聚合酶 σ70全酶结合促进者DNA.
- RNA聚合酶与PmrA的DNA结合域进行静电相互作用,将其重新定向到pmra-box的上游.
- 突变分析证实了DNA识别和RNAPH相互作用残留物对转录活性的重要性.
结论:
- PmrA的识别会诱导DNA的扭曲,而PmrA则促进促进子逃逸,这两者对于转录激活至关重要.
- 这些发现提供了对多素耐药性基因调节机制的见解.
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