The Elp2 Subunit Is Essential for Elongator Complex Assembly and Functional Regulation
The Elp2 Subunit Is Essential for Elongator Complex Assembly and Functional Regulation
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Elp2 亚基对于伸长复合物的组装和功能调节至关重要
DOI：
10.1016/j.str.2015.03.018
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发表时间：
2015-06-02
期刊：
影响因子：
5.7
通讯作者：
Long, Jiafu
中科院分区：
文献类型：
--
作者：
Dong, Chunming;Lin, Zhijie;Long, Jiafu
Elongator是一种高度保守的多蛋白复合物，由6个亚基（Elp 1 -6）组成。Elongator与各种细胞活动有关，并因其在某些神经退行性疾病中的作用而引起临床关注。在这里，我们介绍了Elp 2亚基的晶体结构，揭示了两个七叶片WD 40 β螺旋桨，并通过结构导向突变分析表明，Elp 2的WD 40倍完整性是必要的，它结合到Elp 1和Elp 3亚基在多个物种。详细的生物化学实验表明，在体外和体内，Elp 2通过其保守的碱性残基结合微管。我们发现，这两个相互独立的Elp 2介导的延长器组装和细胞骨架协会是重要的酵母活力。此外，Elp 2的突变极大地影响了Elongator在体内的组蛋白H3乙酰化活性。我们的研究结果表明，Elp 2是一个必要的组成部分，功能延长，并作为一个枢纽，在各种复合物的形成。
Elongator is a highly conserved multiprotein complex composed of six subunits (Elp1-6). Elongator has been associated with various cellular activities and has attracted clinical attention because of its role in certain neurodegenerative diseases. Here, we present the crystal structure of the Elp2 subunit revealing two seven-bladed WD40 beta propellers, and show by structure-guided mutational analyses that the WD40 fold integrity of Elp2 is necessary for its binding to Elp1 and Elp3 subunits in multiple species. The detailed biochemical experiments indicate that Elp2 binds microtubules through its conserved alkaline residues in vitro and in vivo. We find that both the mutually independent Elp2-mediated Elongator assembly and the cytoskeleton association are important for yeast viability. In addition, mutation of Elp2 greatly affects the histone H3 acetylation activity of Elongator in vivo. Our results indicate that Elp2 is a necessary component for functional Elongator and acts as a hub in the formation of various complexes.