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结构性洞察力对冠状病毒尖端倾斜和传染性由链甘氨酸的调节

David Chmielewski¹, Eric A Wilson², Grigore Pintilie³

¹Biophysics Graduate Program, Stanford University, Stanford, CA, 94305, USA.

Nature communications

|November 7, 2023

概括

分析了人类冠状病毒NL63 (HCoV-NL63) 尖端蛋白结构和糖化. 在N1242的N-糖基化会影响尖峰的灵活性和病毒的进入,这表明了治疗点.

科学领域:

病毒学病毒学
结构生物学结构生物学
免疫学免疫学免疫学

背景情况:

冠状病毒使用尖端糖蛋白进入细胞,使其成为疫苗和药物的关键目标.
了解病毒包裹上本地尖蛋白的动态结构对于解释感染性至关重要.

研究的目的:

为了确定人类冠状病毒NL63 (HCoV-NL63) 的原生结构和形状,在病毒体上的尖端蛋白.
调查尖端糖化在HCoV-NL63感染性和免疫逃避中的作用.

主要方法:

低温电子断层扫描 (cryoET) 和亚断层扫描的平均值可用于可视化本地尖结构.
质谱测量以确定特定地点的甘氨酸成分和占用率.
全原子分子动态模拟和传染性测试.

主要成果:

在没有化学固定的情况下,获得了本地HCoV-NL63尖峰形状的详细结构和分布.
与SARS-CoV-2相比,HCoV-NL63尖端表现出较高的寡曼诺糖盾,与增加的免疫逃避相关.
在N1242的糖化被确定为尖峰冠的方向自由和病毒进入的关键.

结论:

这项研究阐明了糖化HCoV-NL63尖端的构造格局,突出了链糖在尖端动态中的作用.
在N1242处的N-糖化是HCoV-NL63感染的关键因素,呈现出潜在的治疗点.

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