Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California-Berkeley, Berkeley, CA 94720, USA.
Structure. 2013 Jun 4;21(6):920-8. doi: 10.1016/j.str.2013.04.002. Epub 2013 Apr 25.
Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans.
真核翻译起始因子 3（eIF3）通过组织 43S 起始前复合物的形成，在蛋白质合成中发挥核心作用。通过电子显微镜的遗传标记可视化，我们揭示了十种人类 eIF3 亚基的分子组织，包括一个八聚体核心。eIF3 的结构与蛋白酶体盖非常相似，具有保守的空间组织，包含 PCI 和 MPN 结构域，协调两个复合物中的功能相互作用。我们进一步表明，eIF3 亚基 a 和 c 与起始因子 eIF1 和 eIF1A 相互作用，这些因子控制起始密码子选择的严格性。最后，我们发现调节信使 RNA 与小核糖体亚基相互作用的亚基 j 与 eIF3 八聚体核心进行多次独立相互作用。这些结果突出了 eIF3 的保守结构以及它如何为包括人类在内的高等真核生物中控制翻译起始的关键因素提供支架。
