MRC Laboratory of Molecular Biology, Cambridge, UK.
Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, CA, USA.
Science. 2020 Sep 4;369(6508):1220-1227. doi: 10.1126/science.aba4904.
A key step in translational initiation is the recruitment of the 43 preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5' end of messenger RNA (mRNA) to form the 48 initiation complex (i.e., the 48). The 48 then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo-electron microscopy to determine the structure of a reconstituted human 48 The structure reveals insights into early events of translation initiation complex assembly, as well as how eIF4F interacts with subunits of eIF3 near the mRNA exit channel in the 43 The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests that downstream mRNA is unwound at least in part by being "pulled" through the 40 subunit during scanning.
翻译起始的一个关键步骤是帽结合复合物(真核起始因子 4F[eIF4F])在信使 RNA(mRNA)的 5'端募集 43 前起始复合物,形成 48 起始复合物(即 48)。然后,48 沿着 mRNA 扫描以定位起始密码子。为了了解所涉及的机制,我们使用冷冻电子显微镜确定了重组的人 48 结构。该结构揭示了翻译起始复合物组装的早期事件的见解,以及 eIF4F 如何与 43 中 mRNA 出口通道附近的 eIF3 亚基相互作用。eIF4F 的位置与 mRNA 募集的开槽模型一致,并表明在扫描过程中,下游 mRNA 至少部分通过“拉动”40 亚基而解旋。