1H, 13C, and 15N backbone chemical shift assignments of m7GTP cap-bound Leishmania initiation factor 4E-1

Anissa Belfetmi,Mélissa Léger-Abraham

doi:10.1007/s12104-020-09958-3

Abstract

Most of the translational control of gene expression in higher eukaryotes occurs during the initiation step of protein synthesis. While this process is well characterized in mammalian cells, it is less defined in parasites, including the ones that cause human Leishmaniasis. The Leishmania cap-binding isoform 1 (LeishIF4E-1) is the only isoform that binds the specific trypanosomatids-specific hypermethylated 5′ cap, called cap-4, in the human stage of the parasite life cycle. We report here the extensive NMR resonance assignment of LeishIF4E-1 bound to a cap analog, m7GTP. The chemical shift data constitute a prerequisite to understanding specific translation initiation mechanisms used in Leishmania parasites and to developing antiparasitic drugs targeting their translation initiation factors.

Highlights

The translation initiation heterotrimeric complex, eIF4F, recruits the 5′ end of mRNAs to the small ribosomal subunit (Shirokikh and Preiss 2018)
A scaffold protein, eIF4G, binds eIF4E, the DEAD-box RNA helicase eIF4A, the poly-A binding protein PABP, and the multisubunit eIF3, which binds to the small ribosomal subunit. eIF4G interacts with eIF4E through a consensus motif, Y(X)4LΦ
The specific factors involved in translation initiation vary depending on the developmental stage of Leishmania parasites

Summary

Introduction

The translation initiation heterotrimeric complex, eIF4F, recruits the 5′ end of mRNAs to the small ribosomal subunit (Shirokikh and Preiss 2018). Keywords Leishmania · Translation initiation · LeishIF4E-1 · NMR Despite our increasing knowledge of translation mechanisms in human cells, how the equivalent process is carried out in trypanosomatids, including Leishmania major, is not as well understood.

Results

Conclusion