Architecture of the yeast Elongator complex.
Architecture of the yeast Elongator complex.
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DOI：
10.15252/embr.201643353
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发表时间：
2017-02
期刊：
影响因子：
7.7
通讯作者：
Müller CW
中科院分区：
文献类型：
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作者：
Dauden MI;Kosinski J;Kolaj-Robin O;Desfosses A;Ori A;Faux C;Hoffmann NA;Onuma OF;Breunig KD;Beck M;Sachse C;Séraphin B;Glatt S;Müller CW
高度保守的真核生物Elongator复合物对tRNA的摆动碱基尿苷进行特异性化学修饰，这对蛋白质组稳定性和稳态是必不可少的。该复合物由六个单独的亚基（Elp 1 - 6）形成，这些亚基对其tRNA修饰活性同样重要。然而，其整体结构和详细的反应机制仍然难以捉摸。在这里，我们报告了完全组装的酵母Elongator和Elp 123子复合物的结构，通过整合结构测定方法解决，显示Elp 1，Elp 2和Elp 3亚基的两个拷贝形成了一个双瓣支架，它不对称地结合Elp 456。我们的拓扑模型是一致的，与以前的研究个别亚基，并进一步验证了互补的生化分析。我们的研究提供了一个关于Elongator如何进行tRNA修饰活性的结构框架。
The highly conserved eukaryotic Elongator complex performs specific chemical modifications on wobble base uridines of tRNAs, which are essential for proteome stability and homeostasis. The complex is formed by six individual subunits (Elp1‐6) that are all equally important for its tRNA modification activity. However, its overall architecture and the detailed reaction mechanism remain elusive. Here, we report the structures of the fully assembled yeast Elongator and the Elp123 sub‐complex solved by an integrative structure determination approach showing that two copies of the Elp1, Elp2, and Elp3 subunits form a two‐lobed scaffold, which binds Elp456 asymmetrically. Our topological models are consistent with previous studies on individual subunits and further validated by complementary biochemical analyses. Our study provides a structural framework on how the tRNA modification activity is carried out by Elongator.