A paralog of lysyl-tRNA synthetase aminoacylates a conserved lysine residue in translation elongation factor P

Nat Struct Mol Biol. 2010 Sep;17(9):1136-43. doi: 10.1038/nsmb.1889. Epub 2010 Aug 22.


Aminoacyl-tRNA synthetase (aaRS) paralogs with unknown functions exist in various species. We now report novel 'protein lysylation' by an Escherichia coli lysyl-tRNA synthetase paralog, GenX/PoxA/YjeA. X-ray crystallographic analysis shows that the structure of the GenX protein resembles that of a class II aaRS. Further in vitro studies reveal that it specifically aminoacylates EF-P with lysine. The shape of the protein substrate mimics that of the L-shaped tRNA, and its lysylation site corresponds to the tRNA 3' end. Thus, we show how the aaRS architecture can be adapted to achieve aminoacylation of a specific protein. Moreover, in vivo analyses reveal that the translation elongation factor P (EF-P) lysylation by GenX is enhanced by YjeK (lysine 2,3-aminomutase paralog), which is encoded next to the EF-P gene, and might convert alpha-lysyl-EF-P to beta-lysyl-EF-P. In vivo analyses indicate that the EF-P modification by GenX and YjeK is essential for cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacylation
  • Animals
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Humans
  • Lysine / metabolism
  • Lysine-tRNA Ligase / chemistry*
  • Lysine-tRNA Ligase / genetics
  • Lysine-tRNA Ligase / metabolism
  • Models, Molecular
  • Mutation
  • Peptide Elongation Factors / chemistry*
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / metabolism
  • Phylogeny
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary


  • Peptide Elongation Factors
  • factor EF-P
  • Lysine-tRNA Ligase
  • Lysine

Associated data

  • PDB/3A5Y
  • PDB/3A5Z