通过F-box域的结合会诱导p97-介导的SCF复合体分解,以激活应激反应程序
Linda Lauinger1, Anna Andronicos2, Karin Flick2
1Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA. llauinge@uci.edu.
Nature communications
|May 8, 2024
概括
F-box域充当环境传感器,检测应力. 这种结合使SCFMet30无酸酶失活,保护细胞免受重金属毒性的影响.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- F-box域是Skp1/Cullin1/F-box蛋白 (SCF) 的一个关键组成部分.
- 其已知的功能是调解与Skp1.1的蛋白质蛋白相互作用.
研究的目的:
- 研究F-box域作为环境传感器的潜在作用.
- 为了确定Met30的F-box域是否能够感知和响应应激.
主要方法:
- 生物化学试验测量与Met30 F-box域的结合.
- 在应力下分析SCFMet30复杂组装和拆卸.
- 研究Met30自流位和其在复杂无活化中的作用.
主要成果:
- Met30 F-box域将与8μM的KD结合在一起,由保存的氨酸残留物介导.
- 结合会诱导一种形状变化,导致Met30的自化.
- 通过Cdc48/p97/VCP招募,Autoubiquitylation触发了SCFMet30的分解,从而使酶失活.
结论:
- F-box 域可以作为环境传感器,而不仅仅是 Skp1 交互模块.
- Met30 F-box域充当直接的传感器,调节SCFMet30的活动.
- 这种调节机制提供了细胞保护,防止引起的压力.
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