通过与核糖体相关的质量控制复合体进行新生链去除的机制
Wenyan Li1, Talia Scheel1, Peter S Shen2
1Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, Utah, USA.
Nature communications
|July 2, 2025
概括
细胞使用与核糖体相关的质量控制 (RQC) 复合体来清除停滞不前的翻译产物. 这项研究揭示了RQC复合体.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 翻译过程中的核糖体停滞会产生不完整的新生链,对蛋白质稳定构成威胁.
- 与核糖体相关的质量控制 (RQC) 复合体对于识别,处理和去除这些异常蛋白质至关重要.
- 在RQC中介的新生链加工和提取的精确机制仍然不完全理解.
研究的目的:
- 阐明由RQC复合体进行新生的链切除的结构和机制基础.
- 调查关键的RQC组件,包括Cdc48,Ufd1-Npl4,Ltn1和Rqc1在清除停滞不前的翻译产品中的作用.
主要方法:
- 电子显微镜 (cryo-EM) 来确定从芽酵母中RQC复合物的结构.
- 生物化学试验分析RQC组件的相互作用和功能.
主要成果:
- 获得了酵母RQC复合物的高分辨率冷EM结构.
- Cdc48 ATPase,以及其 Ufd1-Npl4 适配器,由 Ltn1 E3 泛基因酶招募,从 60S 核糖体子单元中提取.
- Rqc1充当支架,桥接60S子单元,乌比基和Ltn1,从而促进K48结合的多比基链的形成.
结论:
- 该研究提供了一个结构和机制框架,用于通过RQC调解停滞不前的翻译产品的清算.
- 这项工作促进了对细胞蛋白质质量控制途径的理解.
- 这些发现突显了RQC组件在维持蛋白质稳定性方面的协调作用.
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