SARS-CoV-2核体蛋白的二分化域部分失序,形成一个动态的高亲和度二分体
Jasmine Cubuk1,2, J Jeremías Incicco1,3, Kathleen B Hall1
1Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, 660 Euclid Avenue, St. Louis, MO 63110, USA.
概括
SARS-CoV-2 核体蛋白
科学领域:
- 病毒学
- 结构生物学
- 生物物理
背景情况:
- SARS-CoV-2 核体 (N) 蛋白对于病毒基因组的紧缩和包装至关重要.
- 了解N蛋白二聚化是阐明其在病毒复制中的作用的关键.
- 该二元化域的形态动力学并未完全表征.
研究的目的:
- 量化控制SARS-CoV-2 N蛋白质二元体形成的机制.
- 研究N蛋白二元化域的结构和能量.
- 评估二元化对N蛋白的灵活性和功能的影响.
主要方法:
- 使用单分子弗斯特共振能量转移 (smFRET).
- 分析了二元化领域的形态和能量.
- 研究了全长N蛋白的单体和二体状态.
主要成果:
- 单体N蛋白具有扩展的二元化域配置.
- 蛋白质添加稳定了折叠的二元体,具有很高的转移效率 (~12 nM解离常数).
- 模态化是以力驱动的,涉及合折叠和结合.
结论:
- SARS-CoV-2 N 蛋白质二元化是一种稳定,力驱动的过程.
- 二元化域存在于单体状态中的动态组合.
- 保持二元灵活性可能会影响RNA结合和相分离特性.
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