Crystal Structure of Elongator Subcomplex Elp4-6
Crystal Structure of Elongator Subcomplex Elp4-6
复制标题
伸长子复合物 Elp4-6 的晶体结构
DOI：
10.1074/jbc.m112.341560
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发表时间：
2012-06-15
影响因子：
4.8
通讯作者：
Long, Jiafu
中科院分区：
文献类型：
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作者：
Lin, Zhijie;Zhao, Weijing;Long, Jiafu
伸长体是由两个亚复合物Elp1-3和Elp4-6组成的多蛋白复合物。伸长子在酵母和人类之间高度保守，在RNA聚合酶ii介导的转录伸长和许多其他过程中起重要作用，包括细胞骨架组织、胞外分泌和tRNA修饰。在这里，我们确定了酵母Elp4-6亚复合物的晶体结构。Elp4-6的整体结构表明，Elp6是连接Elp4和Elp5的桥梁。详细的结构和序列分析表明，Elp4-6亚复合体的每个亚基形成一个类似reca - atp酶的褶皱，尽管它缺乏atp酶的关键序列特征。位点定向突变和生化分析表明，Elp4-6亚复合物在体外和体内均可组装成六聚体环状结构。此外，GST下拉实验显示，Elp4-6亚复合物的环状组装对其特异性组蛋白H3结合很重要。我们的研究结果可能有助于揭示全息-伸长复合物的底物识别和组装。
Elongator is a multiprotein complex composed of two subcomplexes, Elp1-3 and Elp4-6. Elongator is highly conserved between yeast and humans and plays an important role in RNA polymerase II-mediated transcriptional elongation and many other processes, including cytoskeleton organization, exocytosis, and tRNA modification. Here, we determined the crystal structure of the Elp4-6 subcomplex of yeast. The overall structure of Elp4-6 revealed that Elp6 acts as a bridge to assemble Elp4 and Elp5. Detailed structural and sequence analyses revealed that each subunit in the Elp4-6 subcomplex forms a RecA-ATPase-like fold, although it lacks the key sequence signature of ATPases. Site-directed mutagenesis and biochemical analyses indicated that the Elp4-6 subcomplex can assemble into a hexameric ring-shaped structure in vitro and in vivo. Furthermore, GST pulldown assays showed that the ring-shaped assembly of the Elp4-6 subcomplex is important for its specific histone H3 binding. Our results may shed light on the substrate recognition and assembly of the holo-Elongator complex.