一个全质网络控制了Tom70的结构动态,以协调线粒体进口
Maxwell J Bachochin1, Kelly L McGuire1, Brian D Cook1
1Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Structure (London, England : 1993)
|December 12, 2025
概括
Tom70蛋白质进口到线粒体中涉及不同的开放和闭合构造. 病毒蛋白Orf9b结合改变了这些状态,影响了蛋白质转移动态.
科学领域:
- 线粒体生物学 线粒体生物学
- 蛋白质进口机制是什么
- 结构生物学是结构生物学.
背景情况:
- 姆70通过桥接细胞质伴侣和姆复合体,促进线粒体蛋白质的进口.
- 人类Tom70 (HsTom70c) 的细胞质域分别具有N-终端 (NTD) 和C-终端 (CTD) 域,分别用于伴侣蛋白和前蛋白结合.
- 这些领域之间的通信机制尚未得到充分理解.
研究的目的:
- 阐明 HsTom70c 功能背后的结构机制.
- 调查连接物结合如何影响HsTom70c的形状和动态.
- 了解线粒体蛋白质进口中域间通信的作用.
主要方法:
- 不结合的HsTom70c.的X射线晶体 (2.04 Å分辨率) 的X射线.
- -交换质谱法 (HDX-MS) 用于研究溶液中的结构动力学.
- 分子动力学 (MD) 模拟,主要组件分析 (PCA) 和网络分析.
主要成果:
- 晶体结构显示了HsTom70c的两种不同的构造:开放式和封闭式.
- HDX-MS和MD模拟证实了溶液中这些形状的存在,并确定了NTD和CTD之间的动态连续.
- 将病毒蛋白Orf9b与CTD结合稳定了部分封闭的形状,改变了NTD的动态.
结论:
- HsTom70c存在于通过内部动态网络连接的多种构造.
- 这种网络对于协调伴侣蛋白和前蛋白结合至关重要.
- 病毒蛋白Orf9b结合破坏了这个网络,可能会调节线粒体蛋白质进口通路.
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