在蛋白质折叠中,Hsp70和Hsp110伴侣的合作的结构基础
Sigrun Polier1, Zdravko Dragovic, F Ulrich Hartl
1Department of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Cell
|June 17, 2008
概括
酵母核酸交换因子Sse1p (Hsp110) 与Hsp70直接相互作用,促进ADP释放和必需蛋白质折叠. 这种机制不同于正规的Hsp70s,突出Sse1pp.
科学领域:
- 分子生物学分子生物学
- 蛋白质折叠 蛋白质的折叠
- 结构生物学 结构生物学
背景情况:
- 在蛋白质折叠过程中,hsp70的辅导体至关重要,它们由J域蛋白和核酸交换因子 (NEF) 等辅导体调节.
- NEFs对于从Hsp70中去除ADP至关重要,促进其ATPase循环和伴侣活性.
- 包括酵母Sse1p在内的Hsp110蛋白质与Hsp70s相同,并作为NEFs起作用.
研究的目的:
- 阐明酵母NEF Sse1p在Hsp70.0上促进核酸交换的结构机制.
- 了解Sse1p在Hsp70辅助蛋白质折叠中的作用.
主要方法:
- 使用X射线晶体学来确定Sse1p-Hsp70核酸结合域 (NBD) 复合物的结构.
- 进行了突变分析,以评估Sse1p的NEF活动的功能意义.
主要成果:
- 晶体结构显示Sse1p的ATP结合的NBD和三螺旋束域 (3HBD) 包含Hsp70NBD,诱导其打开和ADP释放.
- 破坏Sse1p的NEF活动的突变被发现是致命的,这证实了它在Hsp70功能中的重要作用.
- 似乎Sse1p通过与正规Hsp70s不同的机制运作,可能涉及直接基质相互作用.
结论:
- Sse1p作为Hsp70的关键NEF,对于蛋白质折叠通过可能涉及直接基质接触的机制至关重要.
- 结构数据提供了关于Hsp110家族成员对Hsp70的全调节的见解.
- 这项研究将Hsp70上的核酸交换定义为Sse1p的一个重要功能,并建议Hsp70辅助折叠的合作模型.
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