冠状病毒M蛋白贩运在上皮细胞中使用了肌Vb拼接变体和Rab10
Lynne A Lapierre1,2,3, Joseph T Roland1,2, Elizabeth H Manning1,2,3
1Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Cells
|January 22, 2024
概括
冠状病毒 (CoV) 的膜蛋白与Myosin Vb (MYO5B+D) 和Rab10相互作用,促进病毒的聚集和贩运. 这种相互作用对M蛋白至关重要.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 膜 (M) 糖蛋白对于冠状病毒 (CoV) 病毒组合至关重要.
- 了解M蛋白相互作用是破译病毒复制机制的关键.
研究的目的:
- 研究小鼠肝炎病毒 (MHV-CoV) 的M蛋白与细胞蛋白之间的相互作用.
- 确定Myosin Vb (MYO5B) 和Rab GTPases在CovM蛋白贩运中的作用.
主要方法:
- 酵母双杂交查,以确定MHV-CoV M蛋白细胞质尾巴的相互作用伙伴.
- 病毒M蛋白和MYO5B+D在人类和狗上皮细胞系中的同时表达.
- 混焦显微镜评估M蛋白,MYO5B+D,Rab10和Rab11a的同定位情况.
- 位点定向突变发生,以确定M蛋白-MYO5B+D相互作用的关键残留物.
- 拉布10的击倒和救援实验.
主要成果:
- MHV-CoV M 蛋白质的细胞质尾巴与 Myosin Vb (MYO5B) 相互作用,特别是 MYO5B+D 拼接变体.
- MYO5B+D与各种CoV (MHV,PEDV,MERS-CoV,SARS-CoV-2) 的M蛋白以及内源Rab10和Rab11a.一起局部化.
- 在M蛋白中的特定点突变,包括MHV-CoV中的E121K和其他CoV中的同源突变,取消了MYO5B+D相互作用和同局部化.
- Rab10的淘汰破坏了M蛋白-MYO5B+D的同定位,可以通过Rab10的再表达来挽救.
结论:
- 冠状病毒的M蛋白利用MYO5B+D和Rab10机制进行细胞内贩运.
- 已识别的相互作用和贩运途径在不同的CoV中保留,包括SARS-CoV-2.
- 针对这种M蛋白与宿主相互作用途径可以为抗病毒开发提供一种策略.
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