严格控制的依赖于核糖体的激活
Alan Brown1, Israel S Fernández1, Yuliya Gordiyenko1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|June 10, 2016
概括
细菌的生存依赖于感知压力. 研究人员在结构上揭示了RelA酶如何结合停滞的核糖体来触发严格的反应,这是一个关键的生存机制,提供了新的抗菌药物标.
科学领域:
- 微生物学
- 分子生物学
- 结构生物学
背景情况:
- 细菌通过应激反应适应环境变化.
- 由于营养缺乏而引发的严格控制, 重新编程了细菌的新陈代谢和基因表达,
- 通过RelA合成的警报激素 (p) pGpp是这种反应的核心.
研究的目的:
- 阐明RelA与停滞的细菌核糖体结合的结构机制.
- 了解RelA如何区分未充电的和氨基酸的tRNA.
- 在抗菌药物开发中提供针对RelA的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定与细菌核糖体结合的RelA的结构.
- 生物化学测定是为了验证结构发现的.
主要成果:
- 冷-EM结构显示了RelA在停滞的核糖体上的独特结合点,与其他转化因子不同.
- RelA的多域架构与扭曲的A位点tRNA相互作用.
- RelA 的TGS 域在固体上阻止了氨基基酸tRNA 的结合,从而促进了 (p) p Gpp 的合成.
结论:
- 该结构解释了被停滞的核糖体激活RelA及其对充电的tRNA的歧视.
- 这种机制启动了严格的反应,对细菌在压力下生存至关重要.
- RelA是开发针对病原细菌的新疗法的一个有希望的目标.
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