Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation.
Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation.
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DOI：
10.1016/j.cell.2009.01.014
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发表时间：
2009-02-06
期刊：
影响因子：
64.5
通讯作者：
Wagner G
中科院分区：
文献类型：
--
作者：
Marintchev A;Edmonds KA;Marintcheva B;Hendrickson E;Oberer M;Suzuki C;Herdy B;Sonenberg N;Wagner G
RNA解旋酶eIF 4A在mRNA解旋和翻译起始期间的扫描中起关键作用。游离eIF 4A是一种弱解旋酶，需要辅助蛋白eIF 4G和eIF 4 H。然而，解旋酶复合物的结构和刺激eIF 4A活性的机制仍然难以捉摸。在这里，我们报告的eIF 4A/4G/4 H解旋酶复合物，这是建立从多个实验观察到的域域接触的拓扑结构。值得注意的是，在解旋酶的ATP结合/水解循环期间，一些相互作用连续重排。我们发现，辅助蛋白调节eIF 4A的ATP的亲和力，同时与两个解旋酶结构域相互作用，促进封闭的，ATP结合的构象或开放的，无核苷酸的构象。复杂的拓扑结构和RNA结合表面的空间排列提供了深入了解它们在刺激解旋酶活性和mRNA解旋和扫描机制中的作用。
The RNA helicase eIF4A plays a key role in unwinding of mRNA and scanning during translation initiation. Free eIF4A is a poor helicase and requires the accessory proteins eIF4G and eIF4H. However, the structure of the helicase complex and the mechanisms of stimulation of eIF4A activity have remained elusive. Here we report the topology of the eIF4A/4G/4H helicase complex, which is built from multiple experimentally observed domain-domain contacts. Remarkably, some of the interactions are continuously rearranged during the ATP binding/hydrolysis cycle of the helicase. We show that the accessory proteins modulate the affinity of eIF4A for ATP by interacting simultaneously with both helicase domains and promoting either the closed, ATP-bound conformation or the open, nucleotide-free conformation. The topology of the complex and the spatial arrangement of the RNA-binding surfaces offer insights into their roles in stimulation of helicase activity and the mechanisms of mRNA unwinding and scanning.
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