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对SARS-CoV-2 NiRAN域的酶可塑性的结构和功能洞察

Gabriel I Small¹, Olga Fedorova², Paul Dominic B Olinares³

¹Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

|October 27, 2023

概括

在SARS-CoV-2的NiRAN域.

科学领域:

生物化学生物化学
结构生物学结构生物学
病毒学病毒学

背景情况:

SARS-CoV-2 尼多病毒 RdRp 关联核样转移酶 (NiRAN) 域对于病毒复制至关重要.
尼兰表现出三种活动:NMPylation,RNAylation和deRNAylation/capping,后两种活动形成病毒RNA 5' cap.
对于这些多样化的NiRAN活动的结构基础仍然不完全理解.

研究的目的:

阐明SARS-CoV-2 NiRAN域的NMPylation和deRNAylation/capping活动背后的结构机制.
为NiRAN反应的催化中间体提供高分辨率的结构洞察力.

主要方法:

使用了高分辨率的冷电子显微镜 (cryo-EM).
确定了NMPylation和deRNAylation/capping反应的催化中间体的结构.

主要成果:

低温电磁结构揭示了NiRAN活动的明显的核酸结合姿势和双价金属离子协调.
脱RNAylation/封闭结构澄清了在封闭反应中对GDP而不是GTP的偏好.
获得了对冠状病毒NiRAN域的乱伦性质的结构性见解.

结论:

这项研究为SARS-CoV-2 NiRAN域的酶功能提供了详细的结构理解.
这些发现为开发针对这种必不可少的病毒酶的治疗方法提供了一个结构性平台.

关键词:

通过NMP化进行了NMP化.尼兰域名 (NiRAN) 是一个域名.这是一种RNA基化.这就是SARS-CoV-2病毒.封闭上限是指封闭上限.冠状病毒冠状病毒的新冠病毒.低温电磁波冷却器 (Cryo-EM) 是一个非常好的方法.这是一种deRNAylation的过程.在 mRNA 封顶上.

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