宿主细胞膜捕获由SARS-CoV-2尖端蛋白融合中间体
Rui Su1, Jin Zeng1, Tara C Marcink2,3
1Department of Chemical Engineering, Columbia University, New York, New York 10027, United States.
ACS central science
|July 3, 2023
概括
这种SARS-CoV-2的尖端蛋白质.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 生物物理学的生物物理.
背景情况:
- SARS-CoV-2 通过尖端蛋白的 S2 子单元介导的融合进入宿主细胞.
- 聚变中间体 (FI) 的结构和动态是未知的,这阻碍了对病毒进入机制的理解.
- 之前的研究缺乏详细的计算模型和膜捕获和融合的确立机制.
研究的目的:
- 构建SARS-CoV-2 S2融合中间体 (FI) 的全长模型.
- 通过分子动力学模拟来研究SARS-CoV-2 FI的动力学和膜相互作用机制.
- 阐明FI灵活性在病毒与宿主膜融合中的作用.
主要方法:
- 从已知的SARS-CoV-2融合前和融合后结构进行推断,以构建一个全长的FI模型.
- 原子和粗粒度分子动力学模拟来分析FI的灵活性和动力学.
- 单独的融合的模拟,以了解它们的膜结合特性.
主要成果:
- SARS-CoV-2 FI 模型表现出了显著的灵活性,具有很大的曲和延伸波动.
- 模拟的FI动态与冷电子断层扫描数据一致,表明膜捕获时间约为2 ms.
- 聚变的N端螺旋促进了膜结合,但其环境在完整的FI中被显著改变.
结论:
- SARS-CoV-2 FI 作为一种机器,利用大规模的配置波动来有效捕获膜.
- 灵活的FI有助于探索目标膜表面,并可能调节聚变动力学.
- 该研究确定了FI的动态性质作为新型抗病毒药物的潜在目标.
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