Structure of translation factor eIF4E bound to m(7)GDP and interaction with 4E-binding protein
Structure of translation factor eIF4E bound to m(7)GDP and interaction with 4E-binding protein
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DOI：
10.1038/nsb0997-717
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发表时间：
1997-09-01
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影响因子：
--
通讯作者：
Wagner, G
中科院分区：
文献类型：
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作者：
Matsuo, H;Li, HJ;Wagner, G
eIF4E，mRNA 帽结合蛋白，是控制真核翻译的主开关。要积极主动。它必须结合 eIF4G 并形成 eIF4F 复合物，其中也包含 eIF4A，通过 eIF4E 与 4E-BP 结合而下调翻译，4E-BP 占据 eIF4G 结合位点，作用于 4E-BP 的信号事件导致其与 eIF4E 解离，然后 eIF4E 可以自由结合 eIF4G 形成活性 eIF4F 复合物。我们已经解析了 CHAPS 胶束中酵母 eIF4E/m(7)Gpp 复合物的结构。我们确定了与 m(7)GpppA 复合物中第二个核苷酸的位置，并鉴定了 4E-BP 结合位点，eIF4E 具有弯曲的八链反向平行 β 折叠，凸面上装饰有三个螺旋，连接环中插入了三个较小的螺旋。帽的 m(7)G 嵌入到凹面的一堆色氨酸中。 4E-BP 结合位点位于包含 β-折叠片边缘、相邻螺旋 a2 和多个不规则二级结构区域的区域。它与帽子结合位点相邻，但不重叠。
eIF4E, the mRNA cap binding protein, is a master switch that controls eukaryotic translation. To be active. it must bind eIF4G and form the eIF4F complex, which also contains eIF4A, Translation is downregulated by association of eIF4E with 4E-BP, which occupies the eIF4G binding site, Signalling events acting on 4E-BP cause it to dissociate from eIF4E, and eIF4E is then free to bind eIF4G to form the active eIF4F complex. We have solved the structure of the yeast eIF4E/m(7)Gpp complex in a CHAPS micelle. We determined the position of the second nucleotide in a complex with m(7)GpppA, and identified the 4E-BP binding site, eIF4E has a curved eight-stranded antiparallel beta-sheet, decorated with three helices on the convex face and three smaller helices inserted in connecting loops. The m(7)G of the cap is intercalated into a stack of tryptophans in the concave face. The 4E-BP binding site is located in a region encompassing one edge of the beta-sheet, the adjacent helix a2 and several regions of non-regular secondary structure. It is adjacent to, but does not overlap the cap-binding site.