无标签地图的多价值结合途径与接体定纳米孔
Hui Ma1, Yongyong Wang1, Ya-Xue Li1
1Molecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.
Journal of the American Chemical Society
|August 24, 2024
概括
这项研究引入了一种新的纳米孔方法来绘制单分子多价值相互作用. 它揭示了对Omicron尖端蛋白和sACE2的度依赖的结合途径,解释了增强的病毒感染力.
科学领域:
- 生物物理
- 分子生物学
- 纳米技术
背景情况:
- 了解多价联体受体相互作用是生物识别的关键.
- 无标签,实时分析短暂的多步绑定事件是一个挑战.
研究的目的:
- 开发一种在单个分子水平上绘制动态多价值相互作用的方法.
- 阐明Omicron尖端蛋白与可溶性ACE2之间的结合途径和亲缘关系.
主要方法:
- 使用联体受体定纳米孔系统进行原生蛋白质分析.
- 使用四态马尔科夫链模型进行动力分析.
- 进行单个单质子单位水平的实时动力分析.
主要成果:
- 对Omicron尖端蛋白 (Omicron S) 和可溶性ACE2 (sACE2) 确定了两个度依赖的结合途径 (顺序和并发).
- 量化了Omicron S1单体和sACE2之间强大的结合亲和力 (-13.1 ± 0.2 kcal/mol).
- 证明 sACE2 与 Omicron S 的结合有助于随后的结合步骤,解决了之前的测量差异.
结论:
- 纳米孔方法可以详细地绘制动态多价值相互作用.
- 通过详细说明其对sACE2的强烈结合,这些发现解释了Omicron的增强感染力.
- 提供针对病毒进入机制的药物设计的见解.
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