在人体冠状病毒中,糖结合会引发突发性开放
Matti F Pronker1, Robert Creutznacher2, Ieva Drulyte3
1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Nature
|October 4, 2023
概括
人类冠状病毒HKU1尖端蛋白在结合糖受体后过渡到开放状态. 这种由异质交叉声驱动的形状变化可能促进免疫逃避和双受体使用.
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 冠状病毒尖端蛋白对于病毒的进入至关重要,也是抗体的关键目标.
- SARS-CoV,SARS-CoV-2和MERS-CoV的尖端蛋白质在主体细胞附着和免疫逃避中动态地切换开放和关闭状态.
- 大多数其他冠状病毒尖端蛋白质都被观察到处于封闭的融合前状态,这表明它们是有规律的开放.
研究的目的:
- 在受体结合时研究人类冠状病毒HKU1尖端蛋白的结构变化.
- 阐明受体结合影响尖端蛋白形状的机制以及病毒进入和免疫逃逸的潜在影响.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定高分辨率结构.
- 分子动力学 (MD) 模拟来分析蛋白质结构动力学.
主要成果:
- 人类冠状病毒HKU1尖端蛋白在与S1A域上的基因受体结合后发生结构变化.
- 受体结合会通过域间通信触发S1B域的开放.
- 这种开放机制与其他贝塔冠状病毒观察到的自发转变不同.
结论:
- 冠状病毒尖端蛋白质的受体诱导的形变化调节病毒的附着.
- 这些发现表明,通过受控的尖端蛋白开放和潜在的双受体利用,免疫规避的机制.
- 这项研究提供了冠状病毒进入和宿主-病原体相互作用的分子基础.
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