Hypusine-containing protein eIF5A promotes translation elongation.
Hypusine-containing protein eIF5A promotes translation elongation.
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DOI：
10.1038/nature08034
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发表时间：
2009-05-07
期刊：
影响因子：
64.8
通讯作者：
Dever, Thomas E.
中科院分区：
文献类型：
--
作者：
Saini, Preeti;Eyler, Daniel E.;Green, Rachel;Dever, Thomas E.
翻译延伸因子促进核糖体的蛋白质合成。先前的研究鉴定了两种普遍保守的翻译延伸因子EF-Tu/eEF 1A和EF-G/eEF 2，其分别将氨酰-tRNA递送到核糖体和促进核糖体易位。eIF 5A因子是真核生物和古细菌中含有不寻常氨基酸羟腐胺赖氨酸[Nε-（4-氨基-2-羟丁基）赖氨酸]的唯一蛋白质，最初是基于其刺激甲硫氨酰-嘌呤霉素合成产率（终点）的能力鉴定的，甲硫氨酰-嘌呤霉素合成是第一个肽键合成的模型测定，被认为报告了翻译起始的某些方面。eIF 5A需要羟腐胺赖氨酸与核糖体结合，并刺激甲硫氨酰嘌呤霉素合成。由于eIF 5A不刺激翻译起始的早期步骤，并且酵母中eIF 5A的耗尽仅适度损害蛋白质合成，因此提出eIF 5A功能限于刺激第一个肽键的合成，或者eIF 5A仅对细胞mRNA的子集起作用。然而，eIF 5A的确切细胞作用尚不清楚，该蛋白也与mRNA衰变（包括无义介导的mRNA衰变（NMD）途径）和核质转运有关。在这里，我们使用分子遗传学和生物化学研究表明，eIF 5A促进翻译延伸。酵母中eIF 5A的缺失或失活导致多聚核糖体的积累和核糖体转运时间的增加。添加来自酵母的重组eIF 5A，而不是缺乏羟腐胺赖氨酸的衍生物，提高了体外三肽合成的速率。此外，eIF 5A的失活模拟了eEF 2抑制剂sordarin的作用，表明eIF 5A可能与eEF 2一起发挥作用，促进核糖体易位。由于eIF 5A是细菌蛋白EF-P的结构同源物，我们提出eIF 5A/EF-P是一个普遍保守的翻译延伸因子。
Translation elongation factors facilitate protein synthesis by the ribosome. Previous studies identified two universally conserved translation elongation factors EF-Tu/eEF1A and EF-G/eEF2 that deliver aminoacyl-tRNAs to the ribosome and promote ribosomal translocation, respectively. The factor eIF5A, the sole protein in eukaryotes and archaea containing the unusual amino acid hypusine [Nε-(4-amino-2-hydroxybutyl)lysine], was originally identified based on its ability to stimulate the yield (endpoint) of methionyl-puromycin synthesis, a model assay for first peptide bond synthesis thought to report on certain aspects of translation initiation. Hypusine is required for eIF5A to associate with ribosomes, and to stimulate methionyl-puromycin synthesis. As eIF5A did not stimulate earlier steps of translation initiation, and depletion of eIF5A in yeast only modestly impaired protein synthesis, it was proposed that eIF5A function was limited to stimulating synthesis of the first peptide bond or that eIF5A functioned on only a subset of cellular mRNAs. However, the precise cellular role of eIF5A is unknown, and the protein has also been linked to mRNA decay, including the nonsense-mediated mRNA decay (NMD) pathway, and to nucleocytoplasmic transport. Here we show using molecular genetic and biochemical studies that eIF5A promotes translation elongation. Depletion or inactivation of eIF5A in yeast resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF5A might function together with eEF2 to promote ribosomal translocation. As eIF5A is a structural homolog of the bacterial protein EF-P, we propose that eIF5A/EF-P is a universally conserved translation elongation factor.
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影响因子：
10.5
作者：
TARUN, SZ;SACHS, AB
通讯作者：
SACHS, AB
影响因子：
5.6
作者：
SCHREIER, MH;ERNI, B;STAEHELIN, T
通讯作者：
STAEHELIN, T
影响因子：
56.9
作者：
DOHMEN, RJ;WU, PP;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
DOI：
10.1073/pnas.95.1.224
发表时间：
1998-01-06
影响因子：
11.1
作者：
Kyrpides, NC;Woese, CR
通讯作者：
Woese, CR
影响因子：
4
作者：
Jao, DLE;Chen, KY
通讯作者：
Chen, KY