细胞转化启动因子2B的晶体结构
Kazuhiro Kashiwagi1,2,3, Mari Takahashi3, Madoka Nishimoto3
1Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|February 23, 2016
概括
科学家确定了真核转化启动因子2B (eIF2B) 的结构,揭示了压力诱导的eIF2α酸化如何产生非生产性复合体,抑制蛋白质合成. 这为细胞应激反应提供了洞察力.
科学领域:
- 分子生物学
- 结构生物学
- 细胞生物学
背景情况:
- 通过抑制真核转化启动因子2B (eIF2B),真核细胞在压力时调节蛋白质合成.
- eIF2B 作为 eIF2 的关氨酸核酸交换因子,对于启动蛋白质合成至关重要.
- 压力诱导的eIF2α酸化抑制了eIF2B活动,这是转化控制的关键机制.
研究的目的:
- 确定eIF2B复合体的三维结构.
- 阐明通过化eIF2α抑制eIF2B的结构基础.
- 为理解压力诱导的转化控制提供结构框架.
主要方法:
- 使用X射线结晶学来确定Schizosaccharomyces pombe eIF2B复合物的结构.
- 基于结构的体外分析,包括表面扫描和位点定向的光交叉链接,确定结合接口.
- 构建了eIF2B-化eIF2α复合物的结构模型.
主要成果:
- 晶体结构揭示了eIF2B异构相的前所未有的安排,其中一个六极管控子复合体结合了两个催化子复合体.
- 在不同的子复合体上确定了eIF2α-binding和eIF2γ-binding接口.
- 化eIF2α与eIF2B结合更强,形成一个抑制eIF2γ核酸交换的非生产性复合体.
结论:
- 确定结构为eIF2B架构提供了详细的分子理解.
- 压力诱导的eIF2α酸化导致非生产性eIF2-eIF2B复合体的形成,停止核酸交换.
- 这项研究提供了eIF2B介导的细胞压力下的蛋白质合成调节的结构基础.
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