美国斯坦福大学医学院Joseph D. Puglisi、圣裘德儿童研究医院Israel S. Fernández等研究人员合作发现，eIF5B和eIF1A调整起始tRNA的方向来允许核糖体亚单位连接。相关论文于2022年6月22日在线发表在《自然》杂志上。

通过结合单分子光谱和结构方法，研究人员使用体外重组系统来研究了人类核糖体亚单位如何结合。单分子荧光显示了普遍保守的真核生物启动因子eIF1A和eIF5B何时与起始复合物结合和脱离。在单分子动力学的指导下，研究人员用单粒子冷冻镜观察了同时包含eIF1A和eIF5B的起始复合体。由此产生的结构显示了真核生物特有的两种蛋白之间的接触是如何重塑起始复合物，使起始氨基酰-tRNA以一种与核糖体亚单位连接相适应的构象定向。

总的来说，这些发现为eIF1A和eIF5B在人类翻译起始过程中的分子编排提供了一个定量和结构框架。

据了解，翻译的起始决定了合成的蛋白质的特性和数量。这一过程在许多人类疾病中都是失调的。一个关键的承诺步骤是当核糖体亚单位在信使RNA上的翻译起始位点结合起来，形成一个功能性的核糖体。

附：英文原文

Title: eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining

Author: Lapointe, Christopher P., Grosely, Rosslyn, Sokabe, Masaaki, Alvarado, Carlos, Wang, Jinfan, Montabana, Elizabeth, Villa, Nancy, Shin, Byung-Sik, Dever, Thomas E., Fraser, Christopher S., Fernndez, Israel S., Puglisi, Joseph D.

Issue&Volume: 2022-06-22

Abstract: Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases1,2. A key commitment step is when the ribosomal subunits join at a translation start site on a messenger RNA to form a functional ribosome. Here, we combined single-molecule spectroscopy and structural methods using an in vitro reconstituted system to examine how the human ribosomal subunits join. Single-molecule fluorescence revealed when the universally conserved eukaryotic initiation factors eIF1A and eIF5B associate with and depart from initiation complexes. Guided by single-molecule dynamics, we visualized initiation complexes that contained both eIF1A and eIF5B using single-particle cryo-electron microscopy. The resulting structure revealed how eukaryote-specific contacts between the two proteins remodel the initiation complex to orient the initiator aminoacyl-tRNA in a conformation compatible with ribosomal subunit joining. Collectively, our findings provide a quantitative and architectural framework for the molecular choreography orchestrated by eIF1A and eIF5B during translation initiation in humans.

DOI: 10.1038/s41586-022-04858-z

Source: https://www.nature.com/articles/s41586-022-04858-z