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首页> 外文期刊>Molecular and Cellular Biology >PKR and GCN2 Kinases and Guanine Nucleotide Exchange Factor Eukaryotic Translation Initiation Factor 2B (eIF2B) Recognize Overlapping Surfaces on eIF2α
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PKR and GCN2 Kinases and Guanine Nucleotide Exchange Factor Eukaryotic Translation Initiation Factor 2B (eIF2B) Recognize Overlapping Surfaces on eIF2α

机译：PKR和GCN2激酶和鸟嘌呤核苷酸交换因子真核翻译起始因子2B（eIF2B）识别eIF2α上的重叠表面

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摘要

Four stress-responsive protein kinases, including GCN2 and PKR, phosphorylate eukaryotic translation initiation factor 2α (eIF2α) on Ser51 to regulate general and gene-specific protein synthesis. Phosphorylated eIF2 is an inhibitor of its guanine nucleotide exchange factor, eIF2B. Mutations that block translational regulation were isolated throughout the N-terminal OB-fold domain in Saccharomyces cerevisiae eIF2α, including those at residues flanking Ser51 and around 20 ? away in the conserved motif K79GYID83. Any mutation at Glu49 or Asp83 blocked translational regulation; however, only a subset of these mutations impaired Ser51 phosphorylation. Substitution of Ala for Asp83 eliminated phosphorylation by GCN2 and PKR both in vivo and in vitro, establishing the critical contributions of remote residues to kinase-substrate recognition. In contrast, mutations that blocked translational regulation but not Ser51 phosphorylation impaired the binding of eIF2B to phosphorylated eIF2α. Thus, two structurally distinct effectors of eIF2 function, eIF2α kinases and eIF2B, have evolved to recognize the same surface and overlapping determinants on eIF2α.
机译：四种应激反应蛋白激酶（包括GCN2和PKR）在Ser51上磷酸化真核翻译起始因子2α（eIF2α），以调节一般的和基因特异性的蛋白合成。磷酸化的eIF2是其鸟嘌呤核苷酸交换因子eIF2B的抑制剂。在啤酒酵母eIF2α的整个N端OB折叠结构域中均分离到了可阻止翻译调控的突变，包括位于Ser51侧翼和20？左右残基的突变。保守的基序K 79 GYID 83 。 Glu49或Asp83的任何突变均会阻止翻译调控。但是，这些突变中只有一部分会破坏Ser51的磷酸化。用Ala取代Asp83可以在体内和体外消除GCN2和PKR的磷酸化作用，从而确定了远程残基对激酶底物识别的关键作用。相反，阻断翻译调控但不阻断Ser51磷酸化的突变会削弱eIF2B与磷酸化eIF2α的结合。因此，eIF2功能的两个结构不同的效应子，eIF2α激酶和eIF2B，已经进化为识别eIF2α上相同的表面和重叠的决定簇。

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