Structure of the eukaryotic initiation factor (eIF) 5 reveals a fold common to several translation factors
Structure of the eukaryotic initiation factor (eIF) 5 reveals a fold common to several translation factors
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DOI：
10.1021/bi052387u
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发表时间：
2006-04-11
期刊：
影响因子：
2.9
通讯作者：
Proud, CG
中科院分区：
文献类型：
--
作者：
Conte, MR;Kelly, G;Proud, CG
真核细胞起始因子5(EIF5)在翻译起始中发挥多种作用。其N-末端作为GTP与eIF2结合的GTP激活蛋白(GAP)，而其C-末端参与多种翻译因子之间的相互作用，包括抑制GTP水解或P-I释放的eIF1和eIF2的β亚基。这些蛋白质及其参与的事件对于在翻译起始过程中准确识别正确的起始密码子至关重要。在这里，我们报告了人eIF5的N-末端结构域的三维溶液结构，包括两个亚域，都使人想起核酸结合模块。N-末端亚区含有“精氨酸指”基序，该基序对GAP功能是必不可少的，但不同寻常的是，它位于分子的部分无序区域。这意味着，在适当的激活信号之后，eIF5的这一部分的构象重新排序可能发生在形成对GTP水解有能力的络合物时。有趣的是，eIF5的N-末端亚域在结构上与eIF2的β亚基的古同源基因相似，并且出人意料地与eIF1相似。这些结果揭示了一个新的蛋白质折叠，该折叠为参与翻译起始相关步骤的几个因子所共有。本文从翻译启动机制的角度讨论了这些观察结果的意义。
Eukaryotic initiation factor 5 (eIF5) plays multiple roles in translation initiation. Its N-terminal domain functions as a GTPase-activator protein (GAP) for GTP bound to eIF2, while its C-terminal region nucleates the interactions between multiple translation factors, including eIF1, which acts to inhibit GTP hydrolysis or P-i release, and the beta subunit of eIF2. These proteins and the events in which they participate are critical for the accurate recognition of the correct start codon during translation initiation. Here, we report the three-dimensional solution structure of the N-terminal domain of human eIF5, comprising two subdomains, both reminiscent of nucleic-acid-binding modules. The N-terminal subdomain contains the "arginine finger" motif that is essential for GAP function but which, unusually, resides in a partially disordered region of the molecule. This implies that a conformational reordering of this portion of eIF5 is likely to occur upon formation of a competent complex for GTP hydrolysis, following the appropriate activation signal. Interestingly, the N-terminal subdomain of eIF5 reveals an alpha/beta fold structurally similar to both the archaeal orthologue of the beta subunit of eIF2 and, unexpectedly, to eIF1. These results reveal a novel protein fold common to several factors involved in related steps of translation initiation. The implications of these observations are discussed in terms of the mechanism of translation initiation.