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首页> 外文期刊>Nucleic Acids Research >Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating P-i release and conformational transitions of the preinitiation complex
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Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating P-i release and conformational transitions of the preinitiation complex

机译：真核翻译起始因子eIF5通过调节预起始复合物的P-i释放和构象转变，提高了起始密码子识别的准确性。

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摘要

eIF5 is the GTPase activating protein (GAP) for the eIF2 center dot GTP center dot Met-tRNA(i)(Met) ternary complex with a critical role in initiation codon selection. Previous work suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the preinitiation complex (PIC) from an open, scanning conformation to a closed state at AUG codons, from which Pi is released from eIF2 center dot GDP center dot P-i. To identify eIF5 functions crucial for accurate initiation, we investigated the consequences of G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R suppressors on these reactions, and on the partitioning of PICs between open and closed states. eIF5-G31R altered regulation of P-i release, accelerating it at UUG while decreasing it at AUG codons, consistent with its ability to stabilize the closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting for its efficient suppression of UUG initiation in G31R, G62S cells; however suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation. The strong defect in GTP hydrolysis conferred by M18V likely explains its broad suppression of Sui(-) mutations in numerous factors. We conclude that both of eIF5' s functions, regulating P-i release and stabilizing the closed PIC conformation, contribute to stringent AUG selection in vivo.
机译：eIF5是eIF2中心点GTP中心点Met-tRNA（i）（Met）三元复合物的GTPase激活蛋白（GAP），在起始密码子选择中起关键作用。先前的工作表明，eIF5突变G31R / SUI5通过增加GAP功能来提高UUG密码子的起始。随后的工作涉及eIF5在AUG密码子从开放，扫描构象到闭合状态的预初始化复合物（PIC）重排中，从eIF2中心点GDP中心点P-i释放Pi。为了鉴定对准确启动至关重要的eIF5功能，我们研究了G31R对GTP水解和Pi释放的影响，以及基因内G31R抑制剂对这些反应以及PIC在打开状态和关闭状态之间的分配的影响。 eIF5-G31R改变了P-i释放的调节，在UUG处加速，而在AUG密码子处降低，这与其稳定UUG封闭复合物的能力相符。抑制剂G62S可以缓解G31R的两个缺陷，这是因为它可以有效抑制G31R，G62S细胞中UUG的启动。但是抑制剂M18V损害了GTP水解，而对PIC构象影响很小。 M18V赋予GTP水解的强烈缺陷可能解释了它在许多因素中对Sui（-）突变的广泛抑制。我们得出的结论是，eIF5的两个功能（调节P-1释放和稳定闭合的PIC构象）均有助于体内严格的AUG选择。

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