SARS-CoV-2 尖峰糖蛋白的结构,功能和抗原性
Alexandra C Walls1, Young-Jun Park1, M Alejandra Tortorici2
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Cell
|March 11, 2020
概括
SARS-CoV-2 尖端蛋白使用 ACE2 进入细胞,类似于 SARS-CoV. 在SARS-CoV-2中独特的素分裂部位
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 出现,对全球健康造成重大影响.
- 冠状病毒尖峰 (S) 糖蛋白对病毒的进入至关重要,也是中和抗体的主要目标.
- 了解SARS-CoV-2 S蛋白质的结构和功能对于开发医学对策至关重要.
研究的目的:
- 调查SARS-CoV-2的细胞进入机制.
- 描述SARS-CoV-2 S糖蛋白的结构特征.
- 探索针对S蛋白的潜在治疗策略.
主要方法:
- 分析SARS-CoV-2 S蛋白与人体 ангиотензин转化酶2 (ACE2) 的相互作用.
- 确定SARS-CoV-2 S ectodomain三元体的冷电子显微镜 (冷EM) 结构.
- 对抗SARS-CoV-2S介导病毒进入的抗体中和的评估.
主要成果:
- SARS-CoV-2 S 使用 ACE2 进入细胞,与 SARS-CoV S 与人类 ACE2 具有相似的结合亲和力.
- 在SARS-CoV-2 S的S1/S2子单元边界发现了一种新型的furin分裂部位,使其与其他冠状病毒区别开来.
- 化EM结构揭示了SARS-CoV-2 S蛋白的三元性外体.
- 针对SARS-CoV S的小鼠多克隆抗体显示出SARS-CoV-2 S介导细胞进入的强有力的抑制.
结论:
- 这些发现为设计针对SARS-CoV-2的疫苗和抑制剂提供了结构蓝图.
- 素分裂部位的存在可能有助于SARS-CoV-2的有效传播.
- 针对保存的S表位体的交叉中和抗体为治疗干预和疫苗接种策略提供了有希望的途径.
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