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人类冠状病毒HKU1尖峰结构揭示了糖特异性和碳水化合物促进的构造变化的基础
Min Jin1, Zaky Hassan1, Zhijie Li2
1Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
Nature communications
|May 5, 2025
概括
人类冠状病毒HKU1通过酸葡萄糖结合物和TMPRSS2.2.与宿主细胞结合. 结构研究揭示了碳水化合物结合时尖端蛋白的明显构造变化,澄清了受体特异性.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 人类冠状病毒HKU1利用糖结合物和跨膜血清蛋白酶2 (TMPRSS2) 进入宿主细胞.
- 病毒与宿主膜融合的精确机制以及HKU1的碳水化合物结合特异性的基础仍然不完全理解.
研究的目的:
- 为了阐明由碳水化合物结合诱导的HKU1尖端蛋白的构造变化.
- 确定HKU1对化体受体的特异性的分子基础.
主要方法:
- 使用高分辨率冷电子显微镜 (cryo-EM) 来确定HKU1尖端蛋白的结构.
- 获得了Apo形式的结构,并与9-O-乙化GD3化物复合.
主要成果:
- HKU1尖端单体表现出四种不同的构造状态,这些状态在与9-O-乙化GD3化物结合后顺序填充.
- 在尖端蛋白中,一个六氨基酸插入物被确定为对化物中发现的9-O-乙化α2-8结合的disialic酸部分的特异性至关重要.
- HKU1在素等诱受体上表现出对9-O-乙化酸的低亲和力.
结论:
- 碳水化合物与HKU1尖端蛋白结合会触发一连串的构造变化,促进TMPRSS2参与和随后的膜融合所需的"向上"构造.
- 已识别的六氨基酸插入是HKU1对类受体的特定识别的关键决定因素,解释了其结合偏好.
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