对D614GSARS-CoV-2尖端蛋白变体的结构和功能分析
Leonid Yurkovetskiy1, Xue Wang2, Kristen E Pascal3
1Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Cell
|September 29, 2020
概括
通过加强病毒进入细胞,SARS-CoV-2 D614G尖端蛋白变体增加了传染性. 这种变异的结构变化促进了ACE2结合和细胞融合,而不会影响抗体中和.
科学领域:
- 病毒学
- 结构生物学
- 分子生物学
背景情况:
- 在全球范围内,SARS-CoV-2尖端 (S) 蛋白变体D614G迅速占主导地位.
- 了解驱动这种变种传播的分子机制至关重要.
研究的目的:
- 调查SARS-CoV-2 D614G尖端蛋白变体的传染性增加的功能和结构基础.
- 将D614G的传染性与各种细胞类型的祖先菌株进行比较.
主要方法:
- 对人类肺部和结肠细胞以及表达ACE2的细胞进行感染性测试.
- 尖端蛋白切割器的冷电子显微镜
- 对ACE2结合亲和力的生物化学分析.
主要成果:
- 在测试的细胞模型中,D614G变异呈现出增强的传染性,包括表达哺乳动物ACE2基因的细胞模型.
- 化EM显示D614G改变了尖端形状,有利于ACE2结合和膜融合.
- 由于分离速度较快,观察到ACE2结合性降低,但感染性增加.
- 对受体结合域的抗体中和功效没有受到影响.
结论:
- D614G突变增强了SARS-CoV-2的传染性,通过促进更开放的尖端形状,有利于ACE2结合和细胞进入.
- D614G尖端蛋白的结构和功能适应解释了其快速的全球传播.
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