人类冠状病毒尖端蛋白的融合前结构
Robert N Kirchdoerfer1, Christopher A Cottrell1, Nianshuang Wang2
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|March 4, 2016
概括
研究人员确定了HKU1冠状病毒尖端蛋白的结构,揭示了它如何结合细胞和融合膜. 这一发现有助于开发针对人类β冠状病毒的干预措施和疫苗.
科学领域:
- 结构生物学
- 病毒学
- 分子生物学
背景情况:
- 人类β型冠状病毒HKU1引起普遍的呼吸系统疾病.
- 像SARS和MERS这样的冠状病毒构成流行病威胁.
- 尖峰 (S) 蛋白决定细胞的热带性和宿主范围.
研究的目的:
- 确定HKU1冠状病毒S蛋白的结构.
- 了解病毒进入和膜融合的分子机制.
- 为设计β冠状病毒疫苗提供基础.
主要方法:
- 单粒子冷电子显微镜 (冷EM).
- 确定了三元蛋白HKU1S的4.0 Å分辨率结构.
主要成果:
- 融合前的结构显示了S1子单位在S2子单位之上,抑制了构造变化.
- 跨位的S1C终端域形成四级相互作用,阻断已知的受体结合表面.
- 它的结构揭示了病毒进入的关键蛋白酶位点.
结论:
- 这些发现支持通过受体结合和蛋白解驱动的S蛋白不稳定化的膜融合模型.
- 该结构是针对β冠状病毒的基于结构的疫苗设计的基础.
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