Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6
Crystal Structure of the Eukaryotic 60S Ribosomal Subunit in Complex with Initiation Factor 6
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DOI：
10.1126/science.1211204
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发表时间：
2011-11-18
期刊：
影响因子：
56.9
通讯作者：
Ban, Nenad
中科院分区：
文献类型：
--
作者：
Klinge, Sebastian;Voigts-Hoffmann, Felix;Ban, Nenad
所有生物体中的蛋白质合成均由核糖体催化。与原核核糖体相比，真核核糖体要大得多，并且受到更复杂的调控。大核糖体亚基 (60S) 催化肽键形成并包含新生多肽出口通道。我们展示了来自嗜热四膜虫的 60S 核糖体亚基与真核起始因子 6 (eIF6) 的复合物，与抗生素放线菌酮（一种真核生物特异性蛋白质合成抑制剂）共结晶，分辨率为 3.5 埃。该结构说明了真核 60S 亚基的复杂功能架构，其中包含真核特异性核糖体蛋白特征和 RNA 扩展片段之间相互作用的复杂网络。它揭示了真核核糖体蛋白元件在活性位点稳定中的作用以及亚基其他功能区域的真核特异性差异的程度。此外，它阐明了与 eIF6 相互作用的分子基础，并为进一步研究核糖体相关疾病和 60S 亚基在蛋白质合成起始中的作用提供了结构框架。
Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.