Mutations in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) that overcome the inhibitory effect of eIF-2 alpha phosphorylation on translation initiation.
Mutations in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha) that overcome the inhibitory effect of eIF-2 alpha phosphorylation on translation initiation.
复制标题
真核翻译起始因子 2 (eIF-2 α) 的 α 亚基发生突变，克服了 eIF-2 α 磷酸化对翻译起始的抑制作用。
DOI：
10.1073/pnas.90.15.7215
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发表时间：
1993
影响因子：
11.1
通讯作者：
A. Hinnebusch
中科院分区：
文献类型：
--
作者：
C. R. Vázquez de Aldana;T. Dever;A. Hinnebusch
在酿酒酵母中，蛋白激酶GCN 2对eIF-2 α的磷酸化导致一般翻译起始的抑制和GCN 4 mRNA翻译的特异性增加。我们分离了eIF-2 α结构基因的突变，这些突变不影响野生型酵母的生长速率，但抑制了GCN 2突变激活形式催化的eIF-2 α过度磷酸化的毒性作用。这些eIF-2 α突变还损害表达野生型GCN 2蛋白的菌株中GCN 4的翻译去阻遏。所有四个突变改变eIF-2 α磷酸化位点40个残基内的单个氨基酸;然而，三个等位基因不降低eIF-2 α磷酸化水平。我们认为这些突变改变了eIF-2和其回收因子真核生物翻译起始因子2B（eIF-2B）之间的相互作用，从而减少了磷酸化eIF-2对eIF-2B在翻译起始中的基本功能的抑制作用。这些突变可以鉴定eIF-2 α中直接参与与eIF-2B的GCN 3亚基的物理相互作用的区域。
Phosphorylation of eIF-2 alpha in Saccharomyces cerevisiae by the protein kinase GCN2 leads to inhibition of general translation initiation and a specific increase in translation of GCN4 mRNA. We isolated mutations in the eIF-2 alpha structural gene that do not affect the growth rate of wild-type yeast but which suppress the toxic effects of eIF-2 alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN2. These eIF-2 alpha mutations also impair translational derepression of GCN4 in strains expressing wild-type GCN2 protein. All four mutations alter single amino acids within 40 residues of the phosphorylation site in eIF-2 alpha; however, three alleles do not decrease the level of eIF-2 alpha phosphorylation. We propose that these mutations alter the interaction between eIF-2 and its recycling factor eukaryotic translation initiation factor 2B (eIF-2B) in a way that diminishes the inhibitory effect of phosphorylated eIF-2 on the essential function of eIF-2B in translation initiation. These mutations may identify a region in eIF-2 alpha that participates directly in a physical interaction with the GCN3 subunit of eIF-2B.