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一个全质网络控制了Tom70的结构动态,以协调线粒体蛋白质进口

Max J Bachochin¹, Kelly L McGuire¹, Brian D Cook¹

¹Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093 USA.

bioRxiv : the preprint server for biology

|August 8, 2025

概括

人类Tom70蛋白 (HsTom70c) 结构显示了开放和闭合的构造,这对于线粒体蛋白质进口至关重要. 病毒蛋白Orf9b的结合改变了这种结构,影响了进口动态,并提供了对Tom70全ostery的见解.

科学领域:

线粒体生物学线粒体生物学
结构生物学是结构生物学.
蛋白质进口的分子机制

背景情况:

姆70对于线粒体蛋白质进口至关重要,它调解了从陪伴体到姆复合体的前蛋白转移.
人类Tom70细胞质域 (HsTom70c) 有N端 (NTD) 和C端 (CTD) 域,但链接机制尚不清楚.

研究的目的:

阐明Tom70功能的结构基础和.
了解病毒蛋白如何与Tom70活动相互作用和调节.

主要方法:

在2.04 Å分辨率下,无线化HsTom70c的X射线晶体学.
-交换质谱 (HDX-MS) 和分子动力学 (MD) 模拟.
主要组件和动态网络分析.

主要成果:

揭示了HsTom70c在晶体结构中的两个不同的构造 (开放式和封闭式),通过域间接触稳定并存在于溶液中.
确定了一个连接NTD和CTD的动态连续,涉及特定的螺旋区域.
证明与CTD结合的病毒蛋白Orf9b稳定了中间形状,并破坏了NTD-CTD动态网络.

结论:

这项研究提供了对Tom70全ostery的第一个结构洞察力,揭示了其功能域之间的动态相互作用.
这些发现为了解Tom70在护送蛋白结合,蛋白质进口和病毒干扰中的作用提供了一个框架.
这里阐明的结构-功能关系是理解线粒体进口调节的关键.

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