A conserved proline triplet in Val-tRNA synthetase and the origin of elongation factor P

Cell Rep. 2014 Oct 23;9(2):476-83. doi: 10.1016/j.celrep.2014.09.008. Epub 2014 Oct 9.


Bacterial ribosomes stall on polyproline stretches and require the elongation factor P (EF-P) to relieve the arrest. Yet it remains unclear why evolution has favored the development of EF-P rather than selecting against the occurrence of polyproline stretches in proteins. We have discovered that only a single polyproline stretch is invariant across all domains of life, namely a proline triplet in ValS, the tRNA synthetase, that charges tRNA(Val) with valine. Here, we show that expression of ValS in vivo and in vitro requires EF-P and demonstrate that the proline triplet located in the active site of ValS is important for efficient charging of tRNA(Val) with valine and preventing formation of mischarged Thr-tRNA(Val) as well as efficient growth of E. coli in vivo. We suggest that the critical role of the proline triplet for ValS activity may explain why bacterial cells coevolved the EF-P rescue system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence*
  • Escherichia coli / chemistry
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Evolution, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptide Elongation Factors / chemistry
  • Peptide Elongation Factors / genetics*
  • Peptide Elongation Factors / metabolism
  • Peptides / genetics*
  • Valine-tRNA Ligase / chemistry
  • Valine-tRNA Ligase / genetics*
  • Valine-tRNA Ligase / metabolism


  • Escherichia coli Proteins
  • Peptide Elongation Factors
  • Peptides
  • factor EF-P
  • polyproline
  • Valine-tRNA Ligase