Comparative sequence and structure analysis of eIF1A and eIF1AD.
Comparative sequence and structure analysis of eIF1A and eIF1AD.
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DOI：
10.1186/s12900-018-0091-6
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发表时间：
2018-09-04
影响因子：
--
通讯作者：
Marintchev A
中科院分区：
文献类型：
--
作者：
Yu J;Marintchev A
真核翻译起始因子1A（eIF 1A）在所有生物中普遍保守。它在翻译起始中具有多种功能，包括核糖体前起始复合物的组装、mRNA结合、扫描和核糖体亚基连接。eIF 1A直接与核糖体小亚基以及其他几种翻译起始因子结合。最近确定了eIF 1A同系物的结构，即含有eIF 1A结构域的蛋白（eIF 1AD），但其生物学功能尚不清楚。由于eIF 1AD具有已知的结构以及其结构和功能已被广泛研究的同源物，因此它是序列和结构分析的非常有吸引力的靶标。eIF 1AD的结构/序列分析发现，在对应于其paraffineIF 1A的核糖体结合表面的表面中具有显著的保守性，包括几乎不变的表面暴露的色氨酸残基，其在eIF 1A与核糖体的相互作用中起重要作用。这些结果表明，eIF 1AD可能与核糖体结合，类似于它的副产物eIF 1A，并且可能在核糖体生物发生或翻译调节中起作用。我们确定了折叠结构域中的保守表面和序列基序以及eIF 1AD的C-末端尾部，这些可能是蛋白质-蛋白质相互作用位点。这些区域对eIF 1AD功能的作用仍有待确定。我们还确定了一组锥虫特异性表面决定簇eIF 1A，这可能是一个有前途的目标，针对这些寄生虫的治疗发展。本文描述的结果确定了eIF 1A和eIF 1AD中可能发挥主要功能作用的区域，并且是有希望的治疗靶点。我们的发现和假设将促进新的研究，并有助于阐明eIF 1AD的功能。
Eukaryotic translation initiation factor 1A (eIF1A) is universally conserved in all organisms. It has multiple functions in translation initiation, including assembly of the ribosomal pre-initiation complexes, mRNA binding, scanning, and ribosomal subunit joining. eIF1A binds directly to the small ribosomal subunit, as well as to several other translation initiation factors. The structure of an eIF1A homolog, the eIF1A domain-containing protein (eIF1AD) was recently determined but its biological functions are unknown. Since eIF1AD has a known structure, as well as a homolog, whose structure and functions have been extensively studied, it is a very attractive target for sequence and structure analysis. Structure/sequence analysis of eIF1AD found significant conservation in the surfaces corresponding to the ribosome-binding surfaces of its paralog eIF1A, including a nearly invariant surface-exposed tryptophan residue, which plays an important role in the interaction of eIF1A with the ribosome. These results indicate that eIF1AD may bind to the ribosome, similar to its paralog eIF1A, and could have roles in ribosome biogenenesis or regulation of translation. We identified conserved surfaces and sequence motifs in the folded domain as well as the C-terminal tail of eIF1AD, which are likely protein-protein interaction sites. The roles of these regions for eIF1AD function remain to be determined. We have also identified a set of trypanosomatid-specific surface determinants in eIF1A that could be a promising target for development of treatments against these parasites. The results described here identify regions in eIF1A and eIF1AD that are likely to play major functional roles and are promising therapeutic targets. Our findings and hypotheses will promote new research and help elucidate the functions of eIF1AD.
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DOI：
10.1126/science.1240585
发表时间：
2013-11-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fernández IS;Bai XC;Hussain T;Kelley AC;Lorsch JR;Ramakrishnan V;Scheres SHW
通讯作者：
Scheres SHW
影响因子：
64.8
作者：
Lomakin, Ivan B.;Steitz, Thomas A.
通讯作者：
Steitz, Thomas A.
影响因子：
64.5
作者：
Hussain T;Llácer JL;Fernández IS;Munoz A;Martin-Marcos P;Savva CG;Lorsch JR;Hinnebusch AG;Ramakrishnan V
通讯作者：
Ramakrishnan V
朝着EIF4F介导的核糖体附着在哺乳动物上限的mRNA上的机理。
影响因子：
10.5
作者：
Kumar P;Hellen CU;Pestova TV
通讯作者：
Pestova TV
影响因子：
16
作者：
Llácer JL;Hussain T;Marler L;Aitken CE;Thakur A;Lorsch JR;Hinnebusch AG;Ramakrishnan V
通讯作者：
Ramakrishnan V