Conserved bipartite motifs in yeast eIF5 and eIF2Bε, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2
Conserved bipartite motifs in yeast eIF5 and eIF2Bε, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2
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DOI：
10.1093/emboj/18.6.1673
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发表时间：
1999-03-15
期刊：
影响因子：
11.4
通讯作者：
Hinnebusch, AG
中科院分区：
文献类型：
--
作者：
Asano, K;Krishnamoorthy, T;Hinnebusch, AG
在真核生物翻译的起始阶段，eIF 5刺激结合在40 S核糖体前起始复合物中的eIF 2上的GTP水解，并且所产生的eIF 2上的GDP被复杂核苷酸交换因子eIF 2B替换为GTP。在这里，我们表明，这些二分图案是重要的，这些因素的结合，在体外和体内，其共同的底物eIF 2的β亚基。我们还发现，在eIF 2 β的N-末端区段中的三个富含赖氨酸的盒介导eIF 2与eIF 5和eIF 2B的结合。因此，eIF 5和eIF 2B β采用相同的序列基序来促进与其共同底物的相同片段的相互作用。与此一致的是，古细菌似乎缺乏eIF 5、eIF 2B和它们的eIF 2 β同系物中这些因子的富含赖氨酸的结合结构域。eIF 5二分蛾对于其通过eIF 3的NIP 1编码的亚基与eIF 3复合物的相互作用也是重要的，因此，eIF 5中的二分基序似乎是多功能的，除了与其底物eIF 2结合外，还通过与eIF 3的相互作用刺激其向40 S前起始复合物的募集。
In the initiation phase of eukaryotic translation, eIF5 stimulates the hydrolysis of GTP bound to eIF2 in the 40S ribosomal pre-initiation complex, and the resultant GDP on eIF2 is replaced with GTP by the complex nucleotide exchange factor, eIF2B, Bipartite motifs rich in aromatic and acidic residues are conserved at the C-termini of eIF5 and the catalytic (epsilon) subunit of eIF2B. Here we show that these bipartite motifs are important for the binding of these factors, both in vitro and in vivo, to the beta subunit of their common substrate eIF2. We also find that three lysine-rich boxes in the N-terminal segment of eIF2 beta mediate the binding of eIF2 to both eIF5 and eIF2B. Thus, eIF5 and eIF2B epsilon employ the same sequence motif to facilitate interaction with the same segment of their common substrate. In agreement with this, archaea appear to lack eIF5, eIF2B and the lysine-rich binding domain for these factors in their eIF2 beta homolog, The eIF5 bipartite moth is also important for its interaction with the eIF3 complex through the NIP1-encoded subunit of eIF3, Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S preinitiation complex through interaction with eIF3 in addition to binding of its substrate eIF2.