Comparative sequence and structure analysis of eIF1A and eIF1AD

Abstract

BackgroundEukaryotic 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.ResultsStructure/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.ConclusionsThe 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.

Genes with evidence of positive selection as potentially related to coloniality and the evolution of morphological features among the lophophorates and entoprocts

“…As the other tree topologies shown in Figure 4d-f provide support for a clade that includes all ectoproct and bryozoan species, these genes may be associated with the differentiation of multiciliated cells. A combined functional synthesis gathered for all of the cellular and developmentally related genes listed here results in some commonalities among their respective roles such as immune response (CNPY4; Takahashi et al, 2007), mRNA processing and translation (EIF1, EIF1AD, and TARDBP; Buratti & Baralle, 2008;Mitchell & Lorsch, 2008;J. Yu & Marintchev, 2018), cell cycle progression, cell proliferation, and cell growth (GADD45GIP1, GHITM, IER5, EIF1, EIF1AD, and USF2; Fujimi & Aruga, 2008;Kwon et al, 2009;Sehrawat et al, 2019;Xiong, Jiang, Liu, Zhou, & Ding, 2019;J.…”

Relevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential

“…Ejection of eIF1 from 40S induces a switch from an open to closed conformation thus probably ending the scanning step [80]. Finally, eIF5B together with eIF1A triggers the dissociation of most remaining eIFs and facilitates the assembly of the 60S ribosomal subunit to form the 80S complex [80,81].…”

“…eIF1AD is an analogue of eIF1A. The role of eIF1AD is still unclear but its analogy with eIF1A suggests its involvement in ribosome biogenesis or protein synthesis [81]. The fact that eIF1AD but not eIF1 or eIF1A, is abnormally expressed in gliomas should encourage studies aiming at elucidating its function, in particular in gliomas.…”