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滑动序列在转位途径的多个点阻碍了26S蛋白酶体

Edwin R Ragwan¹, Faith M Kisker¹, Amelia R Morning¹

¹Department of Chemistry, Villanova University, Villanova, Pennsylvania, USA.

Protein science : a publication of the Protein Society

|May 27, 2024

概括

无素-蛋白酶体系统展开蛋白质进行降解. 这项研究揭示了在折叠域附近的富含甘氨酸的序列如何影响蛋白质展开,这表明在转位过程中存在额外的基质-蛋白酶相互作用.

科学领域:

细胞生物学细胞生物学
分子机制的分子机制
蛋白质降解蛋白质降解

背景情况:

在真核生物中,无素-蛋白酶体系统 (UPS) 降解细胞内蛋白质.
蛋白质被标记为ubiquitin,由26S蛋白质体的19S调节粒子 (RP) 识别,由20S核心粒子 (CP) 展开和降解.
在RP的Rpt子单元上的芳香对于抓住和展开基质蛋白质至关重要.

研究的目的:

为了研究由26S蛋白质组展开基质的空间要求.
确定富含甘氨酸序列的位置如何影响蛋白质展开,特别是在N端附近.
在展开过程中映射基质和蛋白质酶体之间的相互作用间隔.

主要方法:

对富含甘氨酸的肠道位置相对于折叠的蛋白质域进行实验性操纵.
评估这些插入对26S蛋白酶体展开效率的影响.
将受影响区域映射到预测的基质-蛋白酶体相互作用地点.

主要成果:

将富含甘氨酸的序列插入接近折叠域的位置,比放置更远的地方更减少了展开能力.
对展开的最显著的影响发生在与预测的芳香相互作用相对应的位置.
观察到的效应从折叠域扩展到67个氨基酸,表明更广泛的基质-蛋白酶相互作用.

结论:

相对于折叠的域,低复杂度序列的精确间距对于高效的蛋白质体展开至关重要.
除了芳香之外,其他相互作用还通过蛋白酶体通道促进基质转位.
这项研究增强了对控制26S蛋白酶体蛋白质展开和降解的机械力量的理解.

关键词:

这是一种ATP-依赖蛋白酶.发动机蛋白质是一种动力蛋白质.蛋白质酶体蛋白质组是什么蛋白质的展开过程转移转移是指转移的转移.乌比奎丁-蛋白酶体系统

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