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冠状病毒校正核糖核酶的结构和催化多样性

Yu Li¹, Xiaocong Cao², Lauren M Recker¹

¹Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA.

Nature communications

|December 8, 2025

概括

冠状病毒校对酶 (ExoN) 在MERS-CoV和SARS-CoV-2之间有所不同. MERS-CoV ExoN的活性较低,影响病毒突变率和免疫逃避策略.

科学领域:

病毒学病毒学
结构生物学结构生物学
生物化学生物化学

背景情况:

冠状病毒校对外核核酶 (ExoN) 对于病毒基因组稳定性和逃避宿主免疫力至关重要.
了解跨冠状病毒的ExoN的结构和功能分歧是解释突变率,病毒适应性和抗药性变异的关键.

研究的目的:

为了比较分析来自MERS-CoV和SARS-CoV-2的ExoN的结构和催化特性.
阐明这些人类冠状病毒之间Exon活性差异的分子基础.

主要方法:

使用冷电子显微镜 (cryo-EM) 的比较结构分析.
生物化学测试以确定MERS-CoV和SARS-CoV-2外型病毒的催化活性.
对具有多种3'-终端核酸的EXON-RNA复合物的分析.

主要成果:

与SARS-CoV-2 ExoN相比,MERS-CoV ExoN的催化活性明显较低.
化EM结构揭示了这种活性差异的分子基础.
确定了两种对3'-终端核酸切除3'-终端核酸切除3'-终端核酸切除的关键结构元素.

结论:

不同的EXON活动有助于冠状病毒突变率和进化轨迹的变化.
已识别的保存结构决定因素对于病毒RNA校对和免疫规避中的EXON功能至关重要.
这些发现提供了对冠状病毒基因组忠实性和宿主免疫相互作用背后的机制的见解.

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