在2型IRES的翻译启动过程中,核糖体招募的机制
bioRxiv : the preprint server for biology
|June 26, 2025
概括
脑肌心炎病毒 (EMCV) 内部核糖体进入部位 (IRES) 域I结构揭示了与核糖体蛋白质和启动器tRNA的关键相互作用,这对于病毒翻译启动至关重要. 这些发现突显了2型IRES中保留的机制.
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:
- 2型内部核糖体进入点 (IRES),包括脑肌心炎病毒 (EMCV) 的IRES,利用H-L域,并通过其JK域与真核细胞启动因子 (eIF4G/eIF4A) 相互作用.
- 在JK域之前的I域对IRES功能至关重要,但其作用仍然不清楚.
研究的目的:
- 为了阐明驱动EMCVIRES-bound eIF4G/eIF4A的核糖体招募的相互作用.
- 在翻译启动过程中识别由Domain I介导的特定分子接触.
主要方法:
- 确定了EMCV IRES上形成的48S启动复合物的冷电子显微镜 (cryo-EM) 结构.
- 执行功能测试以验证已识别的相互作用的重要性.
主要成果:
- 解析了顶端I域的三叶子结构,显示了通过其Id子域与核糖体蛋白 uS13和 uS19的接触.
- 发现子域 Ic 内必不可少的 GNRA 四环组与启动 tRNA 的 TψC 域直接相互作用.
- 功能性测试证实了这些特定相互作用在IRES中介启动中的关键作用.
结论:
- 域I的尖端结构调解与核糖体蛋白和启动器tRNA的基本相互作用,这对EMCV IRES功能至关重要.
- 在Domain I的顶部保存的结构和相互作用表明,在Type 2 IRES中对核糖体的招募有共同的机制.
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