BACKGROUND 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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eIF1A和eIF1AD的比较序列和结构分析。

背景技术真核翻译起始因子1A（eIF1A）在所有生物中普遍保守。它在翻译起始中具有多种功能，包括核糖体预起始复合物的组装，mRNA结合，扫描和核糖体亚基连接。eIF1A直接与小核糖体亚基以及其他几个翻译起始因子结合。最近确定了eIF1A同源物的结构，即包含eIF1A域的蛋白质（eIF1AD），但其生物学功能尚不清楚。由于eIF1AD具有已知的结构和同系物，其结构和功能已得到广泛研究，因此它是进行序列和结构分析的极具吸引力的目标。结果eIF1AD的结构/序列分析发现，在与其同源物eIF1A的核糖体结合表面相对应的表面上有明显的保守性，包括几乎不变的表面暴露的色氨酸残基，这在eIF1A与核糖体的相互作用中起着重要作用。这些结果表明，eIF1AD可以与其核糖体eIF1A相似地与核糖体结合，并可能在核糖体的生物发生或翻译调控中起作用。我们在eIF1AD的折叠域以及C末端尾部中发现了保守的表面和序列基序，这可能是蛋白质相互作用的位点。这些区域对于eIF1AD功能的作用仍有待确定。我们还确定了eIF1A中的一组锥虫特定表面决定簇，这可能是开发针对这些寄生虫的治疗的有希望的目标。结论此处描述的结果确定了eIF1A和eIF1AD中可能发挥主要功能作用并有望成为治疗靶点的区域。我们的发现和假设将促进新的研究并帮助阐明eIF1AD的功能。