以G4:U69基对向非同源tRNA误电的进化收益
Litao Sun1, Ana Cristina Gomes2, Weiwei He3
1Department of Cell and Molecular Biology, The Scripps Research Institute , La Jolla, California 92037, United States.
Journal of the American Chemical Society
|September 14, 2016
概括
人类细胞可以通过一种特定的酶 (AlaRS) 用氨酸替代蛋白质构成块. 这一发现揭示了真核生物中蛋白质调节的新机制.
科学领域:
- 分子生物学
- 生物化学
- 遗传学
背景情况:
- 由氨基酸-tRNA合成酶控制的转化忠实性对于生物准确性至关重要.
- 转换真实性的修改可以提供监管优势.
研究的目的:
- 研究人类氨酸-tRNA合成酶 (AlaRS) 对氨酸与非同源tRNA错配的能力.
- 确定这种错误充电现象背后的结构和序列决定因素.
主要方法:
- 人类和大肠杆菌AlaRS的比较结构分析.
- 生物化学测试以评估tRNA的错误充电.
- 在tRNA受体茎中分析特定的基对相互作用.
主要成果:
- 人类的AlaRS与大肠杆菌的AlaRS不同,它表现出对包括tRNACys在内的nonalanyl-tRNA产生氨酸的内在能力.
- 在人类细胞中的记者蛋白中观察到囊与氨酸的替代,这与AlaRS错误充电一致.
- 在tRNA受体干中的G4:U69基对对于人类的AlaRS中介误充是必不可少的.
结论:
- 人类的AlaRS具有扩展的tRNA特异性,可以在真核蛋白中进行转录后的氨酸替代.
- 这种在AlaRS中的进化功能增长可能在真核生物中起着调节作用.
- 人类和细菌AlaRS之间的关键序列差异解释了观察到的特定物种的错误充电.
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