富含三氨酸的炭基终端延伸驱动了停滞的多的聚合
Weili Denyse Chang1, Mi-Jeong Yoon1, Kian Hua Yeo1
1School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Molecular cell
|November 2, 2024
概括
停滞的蛋白质翻译可以产生容易聚合的尾巴. 聚氨酸尾巴形成聚合物,播种其他聚氨酸,破坏细胞平衡,并类似于聚氨酸结构.
科学领域:
- 分子生物学分子生物学
- 蛋白质生物化学 蛋白质生物化学
- 细胞蛋白质稳定 细胞蛋白质稳定
背景情况:
- 核糖体可以在受损的mRNA上停滞,导致过早的子单元分裂.
- 分裂的大型核糖体子单元可以继续翻译,将氨酸/氨酸尾巴 (CAT尾巴) 附加到多上.
- 如果没有通过与核糖体相关的质量控制 (RQC) 降解,则形成聚合物.
研究的目的:
- 研究CAT尾巴驱动蛋白质聚合的机制.
- 了解异构的CAT尾巴是如何共同聚合的.
- 探索聚氨酸聚合物形成的细胞后果.
主要方法:
- 在体外聚合试验中使用合成聚氨酸和氨酸丰富.
- 播种实验以评估聚合物形成动力学和异质性.
- 对与聚氨酸聚氨酸聚合物的分子伴侣相互作用的分析.
- 使用酵母模型研究细胞反应,包括蛋白质稳定和热冲击.
主要成果:
- 用C端聚氨酸或氨酸丰富的尾巴形成了耐洗剂的聚合物.
- 这些聚氨酸聚合物对较短,较少富含氨酸的尾巴表现出强烈的播种活性,这解释了异质的CAT尾巴联合聚合.
- 聚氨酸聚合物扣留分子伴侣,破坏蛋白质稳定,并诱导热冲击反应.
- 聚氨酸聚合物可以交叉种子防洗剂聚氨酸聚合物,表明结构相似之处.
结论:
- 聚氨酸和聚氨酸代表了一种新型的聚合易发生的蛋白质图案.
- CAT尾的聚合有助于细胞功能障碍和应激反应.
- 了解这些聚合机制对于细胞蛋白质稳定和疾病研究至关重要.
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