内部分子环控制SARS-CoV-2核体蛋白自我结合和依赖酸化的核酸结合
bioRxiv : the preprint server for biology
|February 6, 2026
概括
SARS-CoV-2核体蛋白酸化通过改变其结构来控制其功能. 酸化使蛋白质紧,抑制RNA结合,但促进细胞内作用的自我关联.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 在SARS-CoV-2核蛋白 (N蛋白) 是必要的病毒组装成核蛋白复合体 (RNP).
- N蛋白在病毒复制和抑制宿主免疫反应中起着至关重要的作用.
- 它的功能是通过酸化Serine/arginine丰富的区域 (SR) 在一个混乱的链接器中进行调节的.
研究的目的:
- 阐明SR区域酸化控制N蛋白功能的分子机制.
- 要了解酸化如何将N蛋白切换到细胞内和病毒组装角色之间.
主要方法:
- 生物物理测量包括水力动力学半径和可逆蛋白自我结合.
- 核酸结合测定和热力学稳定性测量.
- 结构预测和分析已发表的NMR化学转移.
主要成果:
- 一个模型,其中两个相互排斥的分子内环结合N端域 (NTD).
- SR链接物化导致蛋白质紧缩,减少核酸结合,并抑制RNP形成.
- 酸化增强了通过氨酸丰富序列 (LRS) 中的短暂卷曲线的自我关联,有利于细胞内功能.
结论:
- SR链接器酸化动态地改变了N蛋白质的结构和功能.
- 这种依赖酸化的开关使N蛋白能够在病毒复制和组装中扮演不同的角色.
- 这些发现为SARS-CoV-2生命周期和宿主-病原体相互作用的调节提供了洞察力.
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