eIF4B, eIF4G and RNA regulate eIF4A activity in translation initiation by modulating the eIF4A conformational cycle.
eIF4B, eIF4G and RNA regulate eIF4A activity in translation initiation by modulating the eIF4A conformational cycle.
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DOI：
10.1093/nar/gku440
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Klostermeier D
中科院分区：
文献类型：
--
作者：
Harms U;Andreou AZ;Gubaev A;Klostermeier D
真核翻译起始因子eIF 4A是一种DEAD盒解旋酶，在核糖体扫描过程中解析mRNA的5 '-UTR中的二级结构元件。其RNA刺激的ATP酶和ATP依赖性解旋酶活性可被其他翻译起始因子增强，但其潜在机制尚不清楚。在RNA解旋过程中，死亡盒蛋白在开放和闭合构象之间交替。向闭合构象的转变与双链体不稳定有关。eIF 4A是一种特殊的DEAD-box蛋白，可以采用三种不同的构象，即在没有配体的情况下的开放状态、由翻译起始因子eIF 4G稳定的半开放状态以及在eIF 4G和eIF 4 B存在下的闭合状态。我们在这里表明，eIF 4A单独不可测量地采样的闭合构象。翻译起始因子eIF 4 B和eIF 4G加速eIF 4A构象循环。eIF 4G使闭合速率比打开速率增加得更多，而eIF 4 B选择性地增加闭合速率。引人注目的是，eIF 4 B的速率常数和作用对于不同的RNA是不同的，并且与单链区域的存在有关。因此，调节eIF 4A构象循环的动力学对于其活性的多层调节以及其作为翻译起始中的调节中心的作用至关重要。
Eukaryotic translation initiation factor eIF4A is a DEAD-box helicase that resolves secondary structure elements in the 5'-UTR of mRNAs during ribosome scanning. Its RNA-stimulated ATPase and ATP-dependent helicase activities are enhanced by other translation initiation factors, but the underlying mechanisms are unclear. DEAD-box proteins alternate between open and closed conformations during RNA unwinding. The transition to the closed conformation is linked to duplex destabilization. eIF4A is a special DEAD-box protein that can adopt three different conformations, an open state in the absence of ligands, a half-open state stabilized by the translation initiation factor eIF4G and a closed state in the presence of eIF4G and eIF4B. We show here that eIF4A alone does not measurably sample the closed conformation. The translation initiation factors eIF4B and eIF4G accelerate the eIF4A conformational cycle. eIF4G increases the rate of closing more than the opening rate, and eIF4B selectively increases the closing rate. Strikingly, the rate constants and the effect of eIF4B are different for different RNAs, and are related to the presence of single-stranded regions. Modulating the kinetics of the eIF4A conformational cycle is thus central for the multi-layered regulation of its activity, and for its role as a regulatory hub in translation initiation.
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影响因子：
14.9
作者：
Hilbert M;Kebbel F;Gubaev A;Klostermeier D
通讯作者：
Klostermeier D
影响因子：
10.5
作者：
Oberer, M;Marintchev, A;Wagner, G
通讯作者：
Wagner, G
影响因子：
11.4
作者：
ALTMANN, M;MULLER, PP;TRACHSEL, H
通讯作者：
TRACHSEL, H
影响因子：
4.8
作者：
Bi, XP;Goss, DJ
通讯作者：
Goss, DJ
影响因子：
5.4
作者：
Karow, Anne R.;Theissen, Bettina;Klostermeier, Dagmar
通讯作者：
Klostermeier, Dagmar