抑制酵母 pseudouridine-deficient 核糖体的希格罗米辛B 的结构基础
Yu Zhao1, Chong Xu2, Xin Chen3
1Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
Science advances
|April 2, 2025
概括
核细胞核糖体中的伪尿氨酸增强了稳定性,并影响了抗生素易感性. 删除伪尿氨酸会增加对氨基甘油酸 (如B型红素) 的核糖体敏感性.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 细胞核糖体含有伪尿氨酸,一种经过修饰的核酸,特别是在抗生素向区域.
- 伪尿素在核糖体功能和抗生素相互作用中的确切作用仍然不完全理解.
研究的目的:
- 调查伪乌里丁在氨基糖化物介导的翻译抑制中的功能和结构作用.
- 为了比较野生类型酵母核糖体与无伪尿素核糖体,以阐明伪尿素的影响.
主要方法:
- 野生类型和无伪尿素酵母菌核糖体的比较分析.
- 对核糖体热稳定性和对氨基糖化物敏感性的评估.
- 使用模型RNA系统对乙基菌素与核糖体结合的结构研究.
主要成果:
- 无伪尤里丁的核糖体表现出降低的热稳定性和对氨基糖化物增加的敏感性.
- 素B优先结合到无伪乌里丁的核糖体,阻断延长因子eEF2的结合和阻断翻译.
- 结构分析显示,在B2a分单元间的桥梁B2a处结合素B,这与伪尿素的存在和子-抗子双重变形有关.
结论:
- 伪尤里丁有助于核糖体的热稳定性和形状完整性.
- 伪尤里丁的修饰影响了核糖体对氨基糖体抗生素的敏感性,影响了翻译抑制机制.
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