Molecular evolution of protein-RNA mimicry as a mechanism for translational control

Nucleic Acids Res. 2014 Mar;42(5):3261-71. doi: 10.1093/nar/gkt1296. Epub 2013 Dec 13.


Elongation factor P (EF-P) is a conserved ribosome-binding protein that structurally mimics tRNA to enable the synthesis of peptides containing motifs that otherwise would induce translational stalling, including polyproline. In many bacteria, EF-P function requires post-translational modification with (R)-β-lysine by the lysyl-tRNA synthetase paralog PoxA. To investigate how recognition of EF-P by PoxA evolved from tRNA recognition by aminoacyl-tRNA synthetases, we compared the roles of EF-P/PoxA polar contacts with analogous interactions in a closely related tRNA/synthetase complex. PoxA was found to recognize EF-P solely via identity elements in the acceptor loop, the domain of the protein that interacts with the ribosome peptidyl transferase center and mimics the 3'-acceptor stem of tRNA. Although the EF-P acceptor loop residues required for PoxA recognition are highly conserved, their conservation was found to be independent of the phylogenetic distribution of PoxA. This suggests EF-P first evolved tRNA mimicry to optimize interactions with the ribosome, with PoxA-catalyzed aminoacylation evolving later as a secondary mechanism to further improve ribosome binding and translation control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartate-tRNA Ligase / chemistry
  • Aspartate-tRNA Ligase / metabolism
  • Binding Sites
  • Catalytic Domain
  • Evolution, Molecular*
  • Lysine-tRNA Ligase / chemistry*
  • Models, Molecular
  • Molecular Mimicry*
  • Peptide Elongation Factors / chemistry*
  • Peptide Elongation Factors / metabolism
  • Protein Binding
  • Protein Biosynthesis*
  • RNA, Transfer / chemistry
  • RNA, Transfer / metabolism
  • Ribosomes / metabolism
  • Transfer RNA Aminoacylation


  • Peptide Elongation Factors
  • factor EF-P
  • RNA, Transfer
  • Aspartate-tRNA Ligase
  • Lysine-tRNA Ligase