猴痘病毒甲基转移酶 VP39 识别和甲基化 RNA 帽的结构基础。

Structural basis for RNA-cap recognition and methylation by the mpox methyltransferase VP39.

机构信息

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.v.i, Flemingovo nám. 2, 16610, Prague 6, Czech Republic.

出版信息

Antiviral Res. 2023 Aug;216:105663. doi: 10.1016/j.antiviral.2023.105663. Epub 2023 Jul 7.

DOI:10.1016/j.antiviral.2023.105663

PMID:37421984

Abstract

Mpox is a zoonotic disease caused by the mpox virus (MPXV), which has gained attention due to its rapid and widespread transmission, with reports from more than 100 countries. The virus belongs to the Orthopoxvirus genus, which also includes variola virus and vaccinia virus. In poxviruses, the RNA cap is crucial for the translation and stability of viral mRNAs and also for immune evasion. This study presents the crystal structure of the mpox 2'-O-methyltransfarase VP39 in complex with a short cap-0 RNA. The RNA substrate binds to the protein without causing any significant changes to its overall fold and is held in place by a combination of electrostatic interactions, π-π stacking and hydrogen bonding. The structure also explains the mpox VP39 preference for a guanine base at the first position; it reveals that guanine forms a hydrogen bond that an adenine would not be able to form.

摘要

猴痘是一种由猴痘病毒（MPXV）引起的人畜共患疾病，由于其快速广泛传播，引起了广泛关注，已有 100 多个国家报告了病例。该病毒属于正痘病毒属，正痘病毒属还包括天花病毒和牛痘病毒。在痘病毒中，RNA 帽对于病毒 mRNA 的翻译和稳定性以及免疫逃逸至关重要。本研究展示了猴痘 2'-O-甲基转移酶 VP39 与短帽-0 RNA 复合物的晶体结构。该 RNA 底物与蛋白质结合，而不会导致其整体折叠发生任何显著变化，并通过静电相互作用、π-π 堆积和氢键结合固定在适当位置。该结构还解释了猴痘 VP39 对第一位鸟嘌呤碱基的偏好；它表明鸟嘌呤形成了氢键，而腺嘌呤则无法形成。