The In Silico Identification of Potential Members of the Ded1/DDX3 Subfamily of DEAD-Box RNA Helicases from the Protozoan Parasite Leishmania infantum and Their Analyses in Yeast

Genes (Basel). 2021 Feb 1;12(2):212. doi: 10.3390/genes12020212.

Abstract

DEAD-box RNA helicases are ubiquitous proteins found in all kingdoms of life and that are associated with all processes involving RNA. Their central roles in biology make these proteins potential targets for therapeutic or prophylactic drugs. The Ded1/DDX3 subfamily of DEAD-box proteins is of particular interest because of their important role(s) in translation. In this paper, we identified and aligned the protein sequences of 28 different DEAD-box proteins from the kinetoplast-protozoan parasite Leishmania infantum, which is the cause of the visceral form of leishmaniasis that is often lethal if left untreated, and compared them with the consensus sequence derived from DEAD-box proteins in general, and from the Ded1/DDX3 subfamily in particular, from a wide variety of other organisms. We identified three potential homologs of the Ded1/DDX3 subfamily and the equivalent proteins from the related protozoan parasite Trypanosoma brucei, which is the causative agent of sleeping sickness. We subsequently tested these proteins for their ability to complement a yeast strain deleted for the essential DED1 gene. We found that the DEAD-box proteins from Trypanosomatids are highly divergent from other eukaryotes, and consequently they are suitable targets for protein-specific drugs.

Keywords: DEAD-box; Ded1/DDX3; Leishmania; RNA helicase; Saccharomyces cerevisiae; Trypanosoma brucei; leishmaniasis; trypanosomatid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Computer Simulation
  • DEAD-box RNA Helicases / genetics*
  • Humans
  • Leishmania infantum / genetics
  • Leishmania infantum / pathogenicity
  • Protein Biosynthesis / genetics
  • RNA / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Trypanosoma brucei brucei / genetics*
  • Trypanosoma brucei brucei / pathogenicity
  • Trypanosomiasis, African / genetics*
  • Trypanosomiasis, African / parasitology

Substances

  • Saccharomyces cerevisiae Proteins
  • RNA
  • DED1 protein, S cerevisiae
  • DEAD-box RNA Helicases