冠状病毒尖端糖蛋白剪切剂的冷电子显微镜结构
Alexandra C Walls1, M Alejandra Tortorici2,3, Berend-Jan Bosch4
1Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Nature
|February 9, 2016
概括
冠状病毒使用尖端 (S) 糖蛋白三分剂进入细胞. 我们确定了S三元体结构,揭示了其融合前状态和新型冠状病毒疫苗的潜力.
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 冠状病毒构成重大流行病威胁,细胞的进入由尖端 (S) 糖蛋白介导.
- S蛋白对于病毒的进入至关重要,它含有关键的抗原位点,是中和抗体的目标.
研究的目的:
- 为了确定小鼠冠状病毒的S-trimmer ectodomain的结构.
- 阐明S蛋白的融合前结构,并确定稳定相互作用.
- 探索与其他病毒融合蛋白质的机械相似性和进化联系.
主要方法:
- 单粒子冷电子显微镜 (cryo-EM) 的分辨率为4.0 Å.
- 冠状病毒S三元域的结构分析.
主要成果:
- 发现了小鼠冠状病毒S型的转移稳定前融合结构.
- 确定了稳定S三元体的关键相互作用.
- 与帕拉米克索病毒F蛋白质的结构相似性表明它们具有共同的机制和进化起源.
- 保存的融合的可访问性表明潜在的疫苗学策略.
- 与人类冠状病毒S域的比较提供了对物种特异性的见解.
结论:
- 确定的S三元体结构提供了对冠状病毒细胞进入机制的见解.
- 结构数据支持广泛中和抗体和新型冠状病毒疫苗策略的开发.
- 了解S蛋白结构有助于合理化冠状病毒物种的特异性.
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