在二基因酶Cezanne中Lys11-polyubiquitin特异性的分子基础
Tycho E T Mevissen1, Yogesh Kulathu1, Monique P C Mulder2
1Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|October 13, 2016
概括
塞尚二基因酶 (OTUD7B) 专门针对与lys11结合的多基因链. 这种特异性是通过ubiquitin辅助的形状变化实现的,揭示了ubiquitin代码的复杂细节.
科学领域:
- 分子生物学
- 细胞生物学
- 生物化学
背景情况:
- 聚尤比基是一种翻译后的修饰,通过不同的链接来调节多种细胞过程.
- 这种"ubiquitin代码"决定了蛋白质的命运,而duebiquitinating酶 (DUB) 控制了特定的结合类型.
- 卵巢瘤 (OTU) DUBs对于细胞信号传递至关重要,了解它们的特异性是ubiquitin系统的关键.
研究的目的:
- 阐明Cézanne二基因酶 (OTUD7B) 特定识别和分裂Lys11连接的多基因链的机制.
- 通过详细介绍OTU DUB的链接特异性,获得对ubiquitin系统的基本见解.
主要方法:
- 单独使用Cezanne (OTUD7B) 的X射线晶体,并与单双和与Lys11结合的二双复合.
- 交换质谱 (HDX-MS) 用于分析形状变化.
- 酶循环的详细重建.
主要成果:
- 塞尚 (OTUD7B) 对与lys11结合的多基因链具有特异性.
- 在酶激活过程中,乌比基辅助的形状变化是必不可少的.
- 虽然所有多基因链类型都与S1位点结合,但只有Lys11连接的链有效地参与了活性位点的催化循环.
- 这项研究揭示了duibiquitin基质结合时的新型构造状态.
结论:
- 塞尚 (OTUD7B) 采用复杂的机制,涉及基质诱导的形状变化,以达到Lys11结合的特异性.
- 这项工作突显了DUB的动态性质及其活跃部位的可塑性.
- 这些发现提供了关于细胞如何读取和处理特定的泛素代码的详细分子理解.
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