通过HCV IRES介导的eIF3在翻译中的作用的结构洞察力
Wakana Iwasaki1, Kazuhiro Kashiwagi1, Ayako Sakamoto1
1Laboratory for Translation Structural Biology, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
概括
肝炎C病毒 (HCV) 内部核糖体进入点 (IRES) 使用真核细胞启动因子3 (eIF3) 驱动病毒转化. 新的冷EM结构揭示了HCV IRES如何在启动和延伸过程中劫持eIF3以实现有效的病毒蛋白质合成.
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:
- 内部核糖体进入点 (IRES) 在RNA病毒和一些人类基因中启动独立于帽子的翻译.
- 型肝炎病毒 (HCV) IRES利用真核体启动因子3 (eIF3),但其精确的机制仍然难以捉摸.
研究的目的:
- 阐明HCVIRES在翻译过程中与eIF3和核糖体相互作用的结构机制.
- 了解HCVIRES如何克服宿主mRNA竞争并促进病毒翻译.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定HCVIRES-ribosome-eIF3复合体的多重结构.
- 交联质谱法 (XL-MS) 用于分析复合体内的蛋白质-蛋白质相互作用.
主要成果:
- 冷-EM结构显示HCV IRES与核糖体和eIF3同时结合,覆盖启动到延长.
- 型冠状病毒IRES通过紧密结合到子域IIIb来取代eIF3核心子单位.
- 在延长过程中,eIF3非核心子单元与核糖体保持关联,eIF3c-NTD与60S子单元相互作用.
结论:
- HCV IRES使用eIF3不仅用于启动,而且还用于延长和可能重新启动病毒翻译.
- eIF3c-NTD与60S核糖体的相互作用可能对一般的翻译过程至关重要,包括60S连接和eIF3稳定.
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