Abstract
Initiation of translation is the first of the three obligatory steps required for protein synthesis and is carried out by a large number of protein factors called initiation factors in conjunction with ribosomes. One of the key conserved protein factors in eukaryotes that plays a role in this process is eIF4A, which has three homologues in humans with eIF4A1 being the primary factor playing a role in translation initiation. eIF4As are members of the family of DEAD-box helicases that carry out different biological functions. eIF4A1s are recruited to translation initiation complexes via association with eIF4G and have ATP binding, ATP hydrolysis, RNA binding, and unwinding activities. Plasmodium and trypanosomatids such as Leishmania and Trypanosoma are parasites that cause human disease. While mechanistically the function of eIF4A1s in eukaryotes is well-understood, the orthologues peIF4A1s and keIF4A1s in Plasmodium and trypanosomatids are not well-studied. Here, we have used bioinformatics tools and homology modelling/structure prediction to study the motifs and functional signatures of Plasmodium and trypanosomatid peIF4A1s/keIF4A1s. We report a high degree of sequence conservation, structural conservation, and conservation of protein–protein interaction signatures of Plasmodium and trypanosomatid peIF4A1s/keIF4A1s in comparison with human eIF4A1. Thus, in spite of the great divergence in evolution between these parasites and higher eukaryotes, there is remarkable conservation of motifs and functional signatures in Plasmodium and trypanosomatid peIF4A1s/keIF4A1s.
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Acknowledgements
We thank Dr Shubbir Ahmed, All India Institute of Medical Sciences, New Delhi, India, for helpful discussions.
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Conceptualization, data curation, formal analysis, methodology, writing, and reviewing of this manuscript was done by SD. Homology modelling and co-writing of this manuscript was done by AD.
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Corresponding editor: Sudha Bhattacharya
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Dadwal, A., Das, S. Architecture, domain organization, and functional signatures of trypanosomatid keIF4A1s and Plasmodium peIF4A1s suggest conserved functions. J Biosci 48, 44 (2023). https://doi.org/10.1007/s12038-023-00369-9
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DOI: https://doi.org/10.1007/s12038-023-00369-9