ER膜的翻译后蛋白转位机制的结构
Xudong Wu1,2, Cerrone Cabanos1,2, Tom A Rapoport3,4
1Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.
Nature
|January 16, 2019
概括
根据冷EM结构分析,Sec62-Sec63复合体通过打开其侧门来激活Sec61通道进行后翻译蛋白转位. 这种机制有助于缺乏高度疏水信号序列的蛋白质通过.
科学领域:
- 分子生物学
- 结构生物学
- 细胞生物学
背景情况:
- 蛋白质跨膜转移对于细胞功能至关重要,涉及到真核生物中的Sec61通道和原核生物中的SecY通道.
- 信号序列中具有不同疏水性的蛋白质使用不同的转位途径,包括共翻译和后翻译途径.
- 已知Sec62-Sec63复合体在真核生物中介于转化后转位,但Sec61通道激活的机制尚不清楚.
研究的目的:
- 阐明Sec62-Sec63复合体激活Sec61通道进行后翻译蛋白转位的结构机制.
- 确定参与Saccharomyces cerevisiae蛋白转位的完整Sec复合物的结构.
主要方法:
- 使用电子冷显微镜 (cryo-EM) 来确定Sec复合物的高分辨率结构.
- 用生物化学和结构分析来研究Sec61,Sec62,Sec63,Sec71和Sec72蛋白之间的相互作用.
主要成果:
- 结构显示Sec63与Sec61通道直接相互作用,导致其侧门的宽开,而不会移动插头域.
- 这种侧门打开将Sec61通道用于将低疏水性信号序列插入脂质阶段.
- 已证实Sec63的细胞质Brl域阻断核糖体结合并招募Sec71和Sec72,它们参与捕获多.
结论:
- 这项研究为了解Sec62-Sec63复合体如何激活Sec61通道进行后翻译转位提供了结构基础.
- 这些发现揭示了对细胞中蛋白质向至关重要的道关和基质捕获的新机制.
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