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在SARS-CoV-2包膜蛋白中的pH和依赖性芳香网络
João Medeiros-Silva1, Noah H Somberg1, Harrison K Wang1
1Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|April 5, 2022
概括
SARS-CoV-2 E蛋白通道通过芳香网络打开. 酸性pH和离子促进形状变化,增加孔隙宽度和水的可访问性,这表明新型抑制剂的目标.
科学领域:
- 结构生物学 结构生物学
- 病毒学 病毒学
- 生物物理学的生物物理.
背景情况:
- 在SARS-CoV-2的信封 (E) 蛋白质是一种病毒蛋白,对于致病性至关重要.
- 它的跨膜 (TM) 域 (ETM) 形成了离子通道,但打开机制仍然不清楚.
- 了解ETM通道封锁对于开发抗病毒策略至关重要.
研究的目的:
- 在模仿宿主细胞环境的条件下,研究ETM通道孔的结构和动态变化.
- 阐明氨残留在ETM通道封闭中的作用.
- 为了确定SARS-CoV-2抑制剂的潜在目标.
主要方法:
- 使用了固态C和FNMR光谱学.
- 实验是在酸性pH值和离子存在下进行的.
- 分析了ETM的合规动态和水可访问性.
主要成果:
- 酸性pH和Ca2+诱导了终端残留物中的形状障碍和增加了孔水的可访问性.
- ETM 含有三种定期间隔的氨残留物.
- 观察到Phe20和Phe26的两个不同的侧链构造,在水的可访问性和动态上有所不同.
- 管道开放与动态,面向脂质的Phe形状的人群增加相关.
结论:
- 一个复杂的芳香网络,包括氨残留物,调节ETM通道的开放.
- 观察到的形状变化表明了阴离子运输的机制.
- 这种芳香网络代表了开发针对SARS-CoV-2和相关冠状病毒的抑制剂的潜在目标.
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