展开的蛋白质反应信号通过Ire1的高阶组装
Alexei V Korennykh1, Pascal F Egea, Andrei A Korostelev
1Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA. alexei.korennykh@ucsf.edu
Nature
|December 17, 2008
概括
细胞内网膜激酶/核核酶Ire1的寡合化是其功能的关键. 这一过程激活了未折叠的蛋白质反应,从而使mRNA拼接和缓解细胞压力.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 异常的蛋白质折叠在内质网膜 (ER) 中触发了应激反应.
- 酶1 (Ire1) 是ER压力的关键传感器和作用因子.
- Ire1执行HAC1 (酵母) 和XBP1 (甲基动物) 的非传统mRNA拼接,以调节转录因子.
研究的目的:
- 为了研究寡合化对Ire1酶功能的作用.
- 阐明Ire1激活和基质结合的结构基础.
主要方法:
- 获得了Ire1细胞质域的晶体结构.
- 使用一种激酶抑制剂来激活Ire1 RNase活动.
- 分析了Ire1寡合体的结构组合.
主要成果:
- 寡合化是Ire1细胞系域的内在性质.
- 晶体结构揭示了Ire1.1.的新型杆状组件.
- 这种组合促进了转自酸化,对RNase域进行了排序,并创建了一个mRNA结合点.
结论:
- 寡合化是Ire1的双功能激酶/内核酶活性的核心.
- 独特的Ire1结构扩大了对基于激酶的信号机制的理解.
- 通过寡合化激活Ire1对于未折叠的蛋白质反应至关重要.
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