类似于C型肝炎病毒的内部核糖体入口位将eIF3位移,从而进入40S子单元
Yaser Hashem1, Amedee des Georges, Vidya Dhote
11] Howard Hughes Medical Institute (HHMI), Department of Biochemistry and Molecular Biophysics, Columbia University, New York City, New York 10032, USA [2] Department of Biochemistry and Molecular Biophysics, Columbia University, New York City, New York 10032, USA.
Nature
|November 5, 2013
概括
肝炎C病毒 (HCV) 和古典猪瘟病毒 (CSFV) 使用内部核糖体进入点 (IRES) 来进行翻译. 这项研究揭示了eIF3与CSFV IRES的相互作用如何阻止其与40S亚单元结合,有利于病毒mRNA转化.
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:
- 型肝炎病毒 (HCV) 和古典猪瘟病毒 (CSFV) 使用内部核糖体进入点 (IRES) 来启动独立于帽子的翻译.
- 这些IRES需要某种类型的真核启动因子 (eIF),并与40S核糖体子单元相互作用,形成启动复合体.
- 在翻译启动过程中eIF3与HCV类IRES相互作用的具体作用在很大程度上是未知的.
研究的目的:
- 在翻译启动过程中阐明eIF3与HCV类IRES相互作用的功能.
- 研究eIF3与CSFVIRES结合的结构基础及其对核糖体复合体形成的影响.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定含有eIF3和CSFV IRES的40S核糖体复合物的结构.
- 在复合体内分析IRES和eIF3的核糖体位置和相互作用.
主要成果:
- CSFV IRES与40S子单位结合,类似于HCV IRES.
- eIF3从40S子单元上的正规结合点被移开,直接与IRES域III的顶部区域相互作用.
- 这种相互作用阻止了eIF3与40S子单位的关联,从而避免了对绑定站点的竞争.
结论:
- 类似HCV的IRES和eIF3之间的特定相互作用在调节翻译启动方面发挥着至关重要的作用.
- 移位eIF3减轻了40S子单元结合的竞争,并减少了43S预启动复合体的形成.
- 这种机制有利于病毒mRNAs的翻译而不是细胞mRNAs.
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