在哺乳动物细胞中持续的核糖体碰撞应激后翻译重组的可视化
Juliette Fedry1, Joana Silva2, Mihajlo Vanevic3
1Structural Biochemistry, Bijvoet Centre for Biomolecular Research, Utrecht University, 3584 CG Utrecht, the Netherlands; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK.
Molecular cell
|February 10, 2024
概括
缓慢的核糖体会导致碰撞,触发细胞应激反应. 这项研究可视化了哺乳动物细胞中的这些事件,揭示了压缩的多体和新的相互作用部位,为分析翻译动态提供了新的框架.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 核糖体碰撞是影响蛋白质合成的细胞压力信号.
- 之前的研究单独检查了碰撞反应,不清楚它们的集体影响.
研究的目的:
- 想象哺乳动物细胞在持续的核糖体碰撞压力下翻译机制.
- 了解集体碰撞反应对翻译的净后果.
主要方法:
- 低温电子断层扫描被用于对发生碰撞压力的哺乳动物细胞中的核糖体进行成像.
- 分析的重点是多元体结构,核糖体配置和与压力因子的相互作用.
主要成果:
- 持续的碰撞应力压缩多体,高达30%的核糖体形成螺旋状或碰撞的多体.
- 碰撞接口不仅涉及40S子单元,包括L1茎和eEF2,可能会抑制转位.
- 未解决的tRNA-bound 80S,60S和异常的40S状态的积累表明碰撞分辨率的速度限制步骤.
结论:
- 这项研究提供了在持续碰撞压力下翻译机械的现场全球视图.
- 识别了核糖体碰撞的新型结构方面以及细胞反应途径中的潜在瓶.
- 建立了一个框架,用于在压力期间对现场翻译动态的定量分析.
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