病毒RNA的动态调节的双位点相互作用,以捕获宿主翻译启动因子
Shunsuke Imai1, Hiroshi Suzuki2, Yoshinori Fujiyoshi2
1RIKEN Center for Biosystems Dynamics Research, Tsurumi-ku, Yokohama, 230-0045, Japan. shunsuke.imai.ku@riken.jp.
Nature communications
|August 28, 2023
概括
病毒RNA使用内部核糖体进入点 (IRES) 来劫持宿主翻译. 这项研究揭示了脑肌心炎病毒 (EMCV) IRES复合体与宿主因子的结构动态,详细说明了其复杂的对接策略.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- RNA病毒利用内部核糖体进入点 (IRES) 来启动独立于帽子的翻译.
- 脑肌心炎病毒 (EMCV) IRES招募宿主翻译因子,如真核细胞翻译启动因子4G (eIF4G),用于病毒复制.
研究的目的:
- 阐明EMCV IRES复合体与eIF4G和eIF4A的三维结构.
- 研究复杂形成后IRES的动态和构造变化.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定EMCV IRES-eIF4G-eIF4A复合物的结构.
- 使用溶液核磁共振 (NMR) 光谱学来研究IRES领域的动态.
主要成果:
- 在EMCV IRES上确定了两个不同的eIF4G绑定域.
- 复杂的形成改变了这些IRES领域的相对方向.
- 核磁共振揭示了微秒到毫秒的时间尺度上的形态平衡,低人口状态模仿了复杂的结构.
结论:
- 在EMCV IRES采用了复杂的策略,包括构造灵活性,以高效地对接到主机翻译机器.
- 了解这些结构动态,可以了解病毒RNA与宿主蛋白相互作用以及潜在的治疗点.
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