一个非常规的HxD图案编排了依赖于coatomer的冠状病毒形态发生
Surovi Mohona1, Anil K Shakya2, Suruchi Singh2
1Department of Microbiology and Immunology, Loyola University Chicago, Maywood IL, 60153, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
冠状病毒使用一种新型的His-x-Asp (HxD) 信号进行尖端蛋白传输,绕过典型的通路. 这一发现揭示了病毒组合和宿主细胞相互作用的新灵活性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 冠状病毒组装依赖于尖端 (S) 蛋白贩运,通常由双基信号指导.
- 一些人类和模型冠状病毒 (例如,HKU1,OC43,MHV) 缺乏这种正规信号,这对它们的组装构成了难题.
- 了解替代性贩运机制对于破译冠状病毒形态发生至关重要.
研究的目的:
- 为了确定冠状病毒缺乏二基信号的机制,它们的尖端蛋白传输.
- 为了研究一个保存的His-x-Asp (HxD) 序列在尖端蛋白与辅原子相互作用中的作用.
- 为了阐明这种新型相互作用对病毒组合和病毒结构的影响.
主要方法:
- 对His-x-Asp (HxD) 基因和协同体相互作用的结构和生化分析.
- 细胞成像用于跟踪病毒组装期间的尖端蛋白位址.
- 基因操纵以破坏HxD-coatomer相互作用并观察补偿突变.
- 电子显微镜分析病毒形态.
主要成果:
- 保守的His-x-Asp (HxD) 序列在冠状病毒中充当一种非常规的辅酶体结合信号.
- 这种HxD图案通过不同的构造来吸引coatomer子单元,将尖端蛋白引导到M蛋白的组装部位.
- 破坏HxD-coatomer相互作用导致尖端结合受损和补偿性病毒适应.
- 在这种途径中断时,观察到病毒表面结构的变化.
结论:
- 希斯-x-Asp (HxD) 序列是冠状病毒中协同体向的以前未知的动机.
- 冠状病毒组装途径表现出意想不到的灵活性,利用替代宿主细胞机械.
- 这一发现扩大了对病毒形态发生和宿主-病原体相互作用的理解.
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