诺罗病毒由金属离子的可逆激活
Michael Sherman1, Faith Cox1, Hong Smith1
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
Journal of virology
|January 18, 2024
概括
鼠诺病毒 (MNV) 根据pH值,胆盐和金属离子等环境因素而改变形状. 这些可逆的形状变化有助于病毒逃避免疫检测并适应不同的组织.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 鼠类诺病毒 (MNV) 具有由VP1蛋白制成的T=3双象形囊体.
- 突出的 (P) MNV域在对环境刺激的反应中经历了显著的形状变化.
- 这些变化影响受体相互作用和抗体结合.
研究的目的:
- 研究由金属离子诱导的MNV形状变化的结构基础.
- 阐明不同环境刺激对MNV结构的协同效应.
- 了解这些动态变化对病毒逃避和组织适应的影响.
主要方法:
- 低温电子显微镜 (cryo-EM) 在MNV的近原子分辨率 (~2.7 Å) 在Mg2+或Ca2+的存在下.
- 异热定位热量计 (ITC) 用于研究刺激的结合相互作用和协同效应.
- 分析P域,G'H'循环和C'D'循环中的结构变化.
主要成果:
- 金属离子 (Mg2+,Ca2+) 诱导可逆的P域收缩,类似于低pH和胆汁盐.
- 金属离子与G'H'环结合,导致结构重组,暴露了胆盐结合口袋.
- 胆盐,低pH值和金属离子协同作用以稳定激活的病毒结构.
结论:
- MNV表现出独特的动态形状可塑性,根据生理信号适应其结构.
- 这些可逆结构变化对于增强受体相互作用和阻断抗体结合至关重要.
- MNV的动态性质可能有助于免疫逃避和宿主内部的组织特异性适应.
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