在SARS-CoV-2核体蛋白中,一种特定的酸化依赖的构造转换器抑制了RNA结合
Maiia Botova1, Aldo R Camacho-Zarco1, Jacqueline Tognetti1
1Université Grenoble Alpes, CNRS, CEA, IBS, F-38000 Grenoble, France.
Science advances
|August 2, 2024
概括
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 核体蛋白质通过特定酶的过酸化抑制了RNA结合. 这种结构变化对于调节病毒功能和基因组包装至关重要.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 分子机制的分子机制
背景情况:
- SARS-CoV-2 的核体蛋白 (N) 对于封装病毒基因组至关重要.
- 它的氨酸-氨酸丰富 (SR) 域在受感染细胞中经历过酸化,调节功能.
- 过酸化影响N蛋白功能的确切机制尚不清楚.
研究的目的:
- 为了阐明SARS-CoV-2 N蛋白质高酸化的结构后果.
- 研究特定宿主激酶如何调节N蛋白-RNA相互作用.
- 了解酸化在病毒基因组包装和解包装中的作用.
主要方法:
- 核磁共振 (NMR) 光谱被用来监测结构变化.
- 在试验室中使用特定激酶进行了酸化试验:血清氨酸蛋白激酶1 (SRPK1),糖原合成激酶3 (GSK3) 和氨酸激酶1 (CK1).
- 进行了RNA结合试验,以评估酸化对N蛋白-RNA相互作用的影响.
主要成果:
- 通过SRPK1,GSK3和CK1对SR域上的八个特定位点的过酸化取消了RNA结合.
- 酸化诱导结构变化,导致SR域与单链RNA结合相同的接口.
- 蛋白激酶A (PKA) 的酸化没有抑制RNA结合,突出了激酶特异性的调节模式.
- 涉及RNA结合,链接和二元化领域的远程接触被破坏.
结论:
- 由宿主激酶产生的N蛋白高酸化的特定模式直接抑制RNA结合.
- 这种抑制与影响关键功能领域的结构重组有关.
- 这些发现提供了关于调节SARS-CoV-2复制和基因组管理的酶招募的见解.
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