Architecture, domain organization, and functional signatures of trypanosomatid keIF4A1s and peIF4A1s suggest conserved functions.

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. and trypanosomatids such as and are parasites that cause human disease. While mechanistically the function of eIF4A1s in eukaryotes is wellunderstood, the orthologues peIF4A1s and keIF4A1s in 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 and trypanosomatid peIF4A1s/keIF4A1s. We report a high degree of sequence conservation, structural conservation, and conservation of protein-protein interaction signatures of 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 and trypanosomatid peIF4A1s/keIF4A1s.