In eukaryotic translation, termination and ribosome recycling phases are linked to subsequent initiation of a new round of translation by persistence of several factors at ribosomal sub‐complexes. These comprise/include the large eIF3 complex, eIF3j (Hcr1 in yeast) and the ATP‐binding cassette protein ABCE1 (Rli1 in yeast). The ATPase is mainly active as a recycling factor, but it can remain bound to the dissociated 40S subunit until formation of the next 43S pre‐initiation complexes. However, its functional role and native architectural context remains largely enigmatic. Here, we present an architectural inventory of native yeast and human ABCE1‐containing pre‐initiation complexes by cryo‐EM. We found that ABCE1 was mostly associated with early 43S, but also with later 48S phases of initiation. It adopted a novel hybrid conformation of its nucleotide‐binding domains, while interacting with the N‐terminus of eIF3j. Further, eIF3j occupied the mRNA entry channel via its ultimate C‐terminus providing a structural explanation for its antagonistic role with respect to mRNA binding. Overall, the native human samples provide a near‐complete molecular picture of the architecture and sophisticated interaction network of the 43S‐bound eIF3 complex and the eIF2 ternary complex containing the initiator tRNA.

中文翻译：

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天然核糖体 ABCE1-43S 预起始复合物的结构清单

在真核翻译中，终止和核糖体再循环阶段通过核糖体亚复合体中几个因素的持续存在与随后启动新一轮翻译有关。这些包括/包括大型 eIF3 复合物、eIF3j（酵母中的 Hcr1）和 ATP 结合盒蛋白 ABCE1（酵母中的 Rli1）。ATPase 主要作为循环因子具有活性，但它可以保持与解离的 40S 亚基结合，直到形成下一个 43S 预起始复合物。然而，它的功能作用和原生建筑环境在很大程度上仍然是个谜。在这里，我们通过冷冻电镜展示了天然酵母和含有人类 ABCE1 的预起始复合物的结构清单。我们发现 ABCE1 主要与早期 43S 相关，但也与后期 48S 阶段相关。它采用了其核苷酸结合域的新型杂交构象，同时与 eIF3j 的 N 端相互作用。此外，eIF3j 通过其最终的 C 端占据了 mRNA 进入通道，为其在 mRNA 结合方面的拮抗作用提供了结构解释。总体而言，天然人类样本提供了 43S 结合的 eIF3 复合物和包含起始 tRNA 的 eIF2 三元复合物的结构和复杂相互作用网络的近乎完整的分子图。