Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Trends Biochem Sci. 2017 Aug;42(8):589-611. doi: 10.1016/j.tibs.2017.03.004. Epub 2017 Apr 22.
Initiation of translation on eukaryotic mRNAs generally follows the scanning mechanism, wherein a preinitiation complex (PIC) assembled on the small (40S) ribosomal subunit and containing initiator methionyl tRNA (Met-tRNA) scans the mRNA leader for an AUG codon. In a current model, the scanning PIC adopts an open conformation and rearranges to a closed state, with fully accommodated Met-tRNA, upon AUG recognition. Evidence from recent high-resolution structures of PICs assembled with different ligands supports this model and illuminates the molecular functions of eukaryotic initiation factors eIF1, eIF1A, and eIF2 in restricting to AUG codons the transition to the closed conformation. They also reveal that the eIF3 complex interacts with multiple functional sites in the PIC, rationalizing its participation in numerous steps of initiation.
真核生物 mRNA 的翻译起始通常遵循扫描机制，即预起始复合物 (PIC) 组装在小（40S）核糖体亚基上，并包含起始甲硫氨酸 tRNA（Met-tRNA），扫描 mRNA 前导区以寻找 AUG 密码子。在当前模型中，扫描 PIC 采用开放构象，并在识别 AUG 时重新排列为封闭状态，完全容纳 Met-tRNA。来自不同配体组装的 PIC 的最新高分辨率结构的证据支持该模型，并阐明了真核起始因子 eIF1、eIF1A 和 eIF2 将过渡到封闭构象限制在 AUG 密码子上的分子功能。它们还表明，eIF3 复合物与 PIC 中的多个功能位点相互作用，使其能够参与起始的众多步骤。
