甲状腺糖屏蔽的同位素结构和动态特征的犬病毒血蛋白相关的病毒入口和有效的疫苗接种
Hideo Fukuhara1,2, Kohei Yumoto1, Miyuki Sako3
1Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
eLife
|July 24, 2024
概括
狗病毒血蛋白 (CDV-H) 结构显示了一个倾斜的同位体形式. 这种结构,以及动态变化,解释了有效的病毒入口和成功的疫苗接种策略对morbilliviruses.
科学领域:
- 结构生物学是结构生物学.
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 狗病毒 (CDV) 在食肉动物中引起严重的免疫和神经问题.
- CDV血蛋白 (CDV-H) 蛋白通过SLAM和Nectin-4受体调解病毒的进入.
- 病毒融合进入的精确分子机制尚不清楚.
研究的目的:
- 为了确定CDV-H球状头域的晶体结构.
- 阐明Morbillivirus融合和进入背后的分子机制.
- 了解CDV-H与宿主细胞受体相互作用的结构基础.
主要方法:
- 在3.2 Å分辨率下测定CDV-H结构的X射线晶体学.
- 高速原子力显微镜用于实时观察蛋白质动态.
- 与相关的麻疹病毒 (MeV) 等麻疹病毒的序列和结构比较.
主要成果:
- CDV-H结构揭示了一个倾斜的同位体形式,具有六片的β螺旋折叠.
- 确定了SLAM和Nectin-4的受体结合部位,其中的变异表明宿主特异性.
- 广泛的N-链糖化保护蛋白质表面,只暴露受体结合部位.
- 高速原子力显微镜显示了CDV-H二次体的动态形状变化.
结论:
- 倾斜的,糖屏蔽的CDV-H的同位体结构对于有效的融合进入至关重要.
- 在CDV-H的动态形状变化有助于有效的病毒入口和疫苗接种.
- 这些结构和动态特征很可能与其他morbilliviruses共同,影响更广泛的病毒机制和疫苗开发.
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