TMPRSS2和甘氨酸受体协同促进冠状病毒的进入
Haofeng Wang1, Xiaoce Liu1, Xiang Zhang2
1Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
Cell
|July 4, 2024
概括
人类冠状病毒HKU1使用协同机制进入细胞. 对尖端蛋白的结合会导致形状变化,使得TMPRSS2受体能够识别病毒进入.
科学领域:
- 病毒学
- 结构生物学
- 生物化学
背景情况:
- 冠状病毒通过宿主受体的尖端蛋白识别开始进入.
- 人类冠状病毒HKU1 (HCoV-HKU1) 的受体是TMPRSS2和sialoglycans.
- 控制HCoV-HKU1病毒进入的机制在很大程度上是未知的.
研究的目的:
- 阐明HCoV-HKU1进入的分子机制.
- 研究尖端蛋白与受体相互作用的结构基础.
- 了解糖和TMPRSS2在病毒进入中的协同作用.
主要方法:
- 在各种状态 (无活跃,激活甘氨酸,定) 中研究了HCoV-HKU1C尖端蛋白.
- 使用结构分析,突变和结合测试.
- 检查了 HCoV-HKU1A 与 HCoV-HKU1C 的结构.
主要成果:
- 糖结合会诱导尖端NTD的形状变化,使RBD能够识别TMPRSS2.
- 在HCoV-HKU1中发现了一种涉及基和TMPRSS2的协同进入机制.
- HCoV-HKU1 RBD 具有通过三个新型接口识别 TMPRSS2 的插入子域.
- 证实了 HCoV-HKU1 的保留受体识别模式.
结论:
- 病毒的进入涉及基和TMPRSS2之间的协调相互作用,由尖端蛋白的构造变化介导.
- 发现了HCoV-HKU1尖端蛋白对TMPRSS2的新型接口.
- 这些发现为开发新型冠状病毒治疗药物提供了基础.
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