扩展SARS-CoV-2复制和转录复合体的冷EM结构揭示了合成中的中间状态
Liming Yan1, Ji Ge2, Litao Zheng2
1MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China.
Cell
|November 24, 2020
概括
研究人员在mRNA帽合成过程中揭示了SARS-CoV-2复制和转录复合体 (RTC) 的结构. Nsp9 蛋白抑制病毒RNA聚合酶活性,而 nsp12 则表现出对病毒复制至关重要的 guanylyltransferase 功能.
科学领域:
- 病毒学
- 结构生物学
- 分子生物学
背景情况:
- SARS-CoV-2 的 mRNA 转录依赖于复制和转录复合体 (RTC).
- 了解RTC的结构是抑制病毒复制的关键.
研究的目的:
- 在mRNA帽结构合成过程中阐明SARS-CoV-2RTC的结构基础.
- 确定抗病毒药物开发的潜在目标.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定扩展RTC的原子结构.
- 生物化学测试以描述蛋白质-RNA相互作用和酶活动.
主要成果:
- 确定了扩展的SARS-CoV-2 RTC (nsp7-nsp82-nsp12-nsp132-RNA) 与nsp9的冷EM结构.
- Nsp9与nsp12 (RdRp) NiRAN结合,抑制其催化活性.
- Nsp12 NiRAN表现出甘转移酶的活性,形成了GpppA盖的核心结构.
- Nsp13经历了形状变化,将其指插入模板原始RNA中.
结论:
- 这项研究揭示了RTC对于mRNA合成至关重要的中间状态.
- 这些发现为RTC架构和潜在的抗病毒目标提供了洞察力.
- Nsp9的抑制作用和nsp12的酶活性为治疗提供了途径.
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