Protein glutaminylation is a yeast-specific posttranslational modification of elongation factor 1A

J Biol Chem. 2017 Sep 29;292(39):16014-16023. doi: 10.1074/jbc.M117.801035. Epub 2017 Aug 11.

Abstract

Ribosomal translation factors are fundamental for protein synthesis and highly conserved in all kingdoms of life. The essential eukaryotic elongation factor 1A (eEF1A) delivers aminoacyl tRNAs to the A-site of the translating 80S ribosome. Several studies have revealed that eEF1A is posttranslationally modified. Using MS analysis, site-directed mutagenesis, and X-ray structural data analysis of Saccharomyces cerevisiae eEF1A, we identified a posttranslational modification in which the α amino group of mono-l-glutamine is covalently linked to the side chain of glutamate 45 in eEF1A. The MS analysis suggested that all eEF1A molecules are modified by this glutaminylation and that this posttranslational modification occurs at all stages of yeast growth. The mutational studies revealed that this glutaminylation is not essential for the normal functions of eEF1A in S. cerevisiae However, eEF1A glutaminylation slightly reduced growth under antibiotic-induced translational stress conditions. Moreover, we identified the same posttranslational modification in eEF1A from Schizosaccharomyces pombe but not in various other eukaryotic organisms tested despite strict conservation of the Glu45 residue among these organisms. We therefore conclude that eEF1A glutaminylation is a yeast-specific posttranslational modification that appears to influence protein translation.

Keywords: GTPase; Saccharomyces cerevisiae; Schizosaccharomyces pombe; eukaryotic elongation factor eEF1A; glutaminylation; helix A*–loop–helix A′ region; posttranslational modification (PTM); protein synthesis; switch I region; translation elongation factor.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Aminoacylation / drug effects
  • Anti-Infective Agents / pharmacology
  • Conserved Sequence
  • Crystallography, X-Ray
  • Databases, Protein
  • Gene Expression Regulation, Fungal / drug effects
  • Glutamic Acid / metabolism
  • Glutamine / metabolism*
  • Helix-Loop-Helix Motifs
  • Models, Molecular*
  • Mutagenesis, Site-Directed
  • Mutation
  • Peptide Elongation Factor 1 / chemistry
  • Peptide Elongation Factor 1 / genetics
  • Peptide Elongation Factor 1 / metabolism*
  • Protein Processing, Post-Translational* / drug effects
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment
  • Species Specificity

Substances

  • Anti-Infective Agents
  • Peptide Elongation Factor 1
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • TEF2 protein, S cerevisiae
  • Glutamine
  • Glutamic Acid

Associated data

  • PDB/1F60
  • PDB/5O8W
  • PDB/4C0S
  • PDB/3WXM
  • PDB/1SKQ
  • PDB/1IJF