一种进化保守的机制通过pH感应区域控制着pyruvate kinase的可逆性粉样蛋白
Gea Cereghetti1, Vera M Kissling2, Lisa M Koch3
1Institute of Biochemistry, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, CB2 1EW Cambridge, UK.
Developmental cell
|May 24, 2024
概括
功能性粉样蛋白,如酸盐激酶 (PK),通过pH敏感核心可逆聚合. 这种机制在各种物种中保持,在压力期间调节细胞代谢.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 粉样蛋白通常是与神经退行性疾病相关的不可逆转的聚合物.
- 粉样蛋白的一小部分是功能性的和可逆的,但它们的调节是不太了解的.
研究的目的:
- 调查粉样蛋白可逆性的保存机制.
- 检查pH在调节功能性粉样蛋白形成中的作用.
主要方法:
- 在酵母和人体细胞中研究了酸盐激酶 (PK).
- 利用基因突变来探测特定残留在聚合中的作用.
- 分析了PK聚合对细胞代谢和生长的影响.
主要成果:
- 酵母和人类PK形成可逆的,对pH敏感的粉样蛋白.
- 细胞酸盐酸化通过关键残留物的质子化触发聚合.
- 影响质子位点的突变控制了PK的溶解性和聚合性.
- 基因聚合与代谢重新连接和糖溶解停止有关.
结论:
- 确定了功能性粉样蛋白调节的进化保守的,pH值依赖的机制.
- 这种机制区分了功能性粉样蛋白和病态聚合物.
- 错误调节PK聚合导致严重的生长缺陷.
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