Taking a re-look at cap-binding signatures of the mRNA cap-binding protein eIF4E orthologues in trypanosomatids
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Taking a re-look at cap-binding signatures of the mRNA cap-binding protein eIF4E orthologues in trypanosomatids Supratik Das1 Received: 31 May 2020 / Accepted: 31 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Protein translation leading to polypeptide synthesis involves three distinct events, namely, initiation, elongation, and termination. Translation initiation is a multi-step process that is carried out by ribosomes on the mRNA with the assistance of a large number of proteins called translation initiation factors. Trypanosomatids are kinetoplastidas (flagellated protozoans), some of which cause acute disease syndromes in humans. Vector-borne transmission of protozoan parasites like Leishmania and Trypanosoma causes diseases that affect a large section of the world population and lead to significant morbidity and mortality. The mechanisms of translation initiation in higher eukaryotes are relatively well understood. However, structural and functional conservation of initiation factors in trypanosomatids are only beginning to be understood. Studies carried out so far suggests that at least in Leishmania and Trypanosoma eIF4E function may not be restricted to canonical translation initiation and some of the homologues may have alternate/non-canonical functions. Nonetheless, all of them bind the cap analogs, albeit with different efficiencies, indicating that this property may play an important role in the functionality of eIF4Es. Here, I give a brief background of trypanosomatid eIF4Es and revisit the cap-binding signatures of eIF4E orthologues in trypanosomatids, whose genome sequences are available, in detail, in comparison to human eIF4E1 and Trypanosoma cruzi eIF4E5, with an expanded list of members of this group in light of newer findings. The group 1 and 2 eIF4Es may use either a variation of heIF4E1 or T. cruzi eIF4E5 cap-4-binding signatures, while eIF4E5 and eIF4E6 use distinct amino acid contacts. Keywords Trypanosomatids · Pathogenic protozoan parasites · Protein synthesis · Translation initiation · eIF4E · Orthologues · mRNA cap · cap-4
Introduction Kinetoplastids are flagellated protozoans which have a DNAcontaining region called kinetoplast in their mitochondrion [1]. Trypanosomatids are a family of kinetoplastids that can parasitize different animals as well as plants and insects [1, 2]. They can be monoxenous (one host) or dixenous (two hosts), the latter being transmitted through an insect host [2]. Not all kinetoplastids are trypanosomatids e.g., the freeliving bodonid Bodo saltans [3]. Of these, trypanosomatids of the genera Leishmania and Trypanosoma are obligatory parasites in vertebrates including humans [1, 2], while some species of the Phytomonas genera cause plant disease [4]. * Supratik Das [email protected] 1
Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad‑Gurgaon Expressway, PO Box #04, Faridabad, Haryana 121001, India
Plant trypanosomatids are morphologically distinct
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