Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major

Shimi Meleppattu, Haribabu Arthanari, Alexandra Zinoviev, Andras Boeszoermenyi, Gerhard Wagner, Michal Shapira, Mélissa Léger-Abraham

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Leishmania parasites are unicellular pathogens that are transmitted to humans through the bite of infected sandflies. Most of the regulation of their gene expression occurs post-transcriptionally, and the different patterns of gene expression required throughout the parasites' life cycle are regulated at the level of translation. Here, we report the X-ray crystal structure of the Leishmania cap-binding isoform 1, LeishIF4E-1, bound to a protein fragment of previously unknown function, Leish4E-IP1, that binds tightly to LeishIF4E-1. The molecular structure, coupled to NMR spectroscopy experiments and in vitro cap-binding assays, reveal that Leish4E-IP1 allosterically destabilizes the binding of LeishIF4E-1 to the 5' mRNA cap. We propose mechanisms through which Leish4E-IP1-mediated LeishIF4E-1 inhibition could regulate translation initiation in the human parasite.

Original languageEnglish
Pages (from-to)3791-3801
Number of pages11
JournalNucleic Acids Research
Volume46
Issue number7
DOIs
StatePublished - 20 Apr 2018

ASJC Scopus subject areas

  • Genetics

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