在SARS-CoV-2外核酶和甲基转移酶复合体中的铁硫:对于病毒基因组校对和封闭的相关性
Nunziata Maio1, Umberto Terranova2, Yan Li3
1Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA. nunziata.maio@nih.gov.
Nature communications
|August 15, 2025
概括
冠状病毒在RNA处理的关键酶中使用铁硫. 这些集群调节甲基转移酶活性,影响病毒复制,并建议新的治疗点.
科学领域:
- 生物化学 生物化学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 冠状病毒利用复制-转录复合体进行基因组复制.
- 像nsp14和nsp10这样的关键酶对于病毒RNA处理至关重要,包括外核酶和甲基转移酶活动.
研究的目的:
- 调查共因子在冠状病毒RNA处理酶中的作用.
- 阐明nsp14和nsp10中的铁硫团的结构和功能意义.
主要方法:
- 无氧净化nsp14和nsp10以合 [Fe4S4] 集群.
- 量子力学/分子力学模拟和氧化还原定位.
- 测试用于测量RNA结合和酶活性 (甲基转移酶,外核酶).
主要成果:
- Nsp14和nsp10合物[Fe4S4]集群而不是中心.
- 铁硫氧化状态调节RNA结合亲和力.
- 铁硫集群增强nsp14和nsp10/nsp16甲基转移酶活动,但不增强ExoN活动.
结论:
- 在SARS-CoV-2RNA处理中发现了铁硫集群的氧化还原调节功能.
- 表明病毒酶功能是由Fe-S辅因子还氧化状态调节的.
- 突出了针对氧化还原敏感病毒机制的潜力.
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