Arginine-rhamnosylation as new strategy to activate translation elongation factor P

Nat Chem Biol. 2015 Apr;11(4):266-70. doi: 10.1038/nchembio.1751. Epub 2015 Feb 16.


Ribosome stalling at polyproline stretches is common and fundamental. In bacteria, translation elongation factor P (EF-P) rescues such stalled ribosomes, but only when it is post-translationally activated. In Escherichia coli, activation of EF-P is achieved by (R)-β-lysinylation and hydroxylation of a conserved lysine. Here we have unveiled a markedly different modification strategy in which a conserved arginine of EF-P is rhamnosylated by a glycosyltransferase (EarP) using dTDP-L-rhamnose as a substrate. This is to our knowledge the first report of N-linked protein glycosylation on arginine in bacteria and the first example in which a glycosylated side chain of a translation elongation factor is essential for function. Arginine-rhamnosylation of EF-P also occurs in clinically relevant bacteria such as Pseudomonas aeruginosa. We demonstrate that the modification is needed to develop pathogenicity, making EarP and dTDP-L-rhamnose-biosynthesizing enzymes ideal targets for antibiotic development.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Arginine / chemistry*
  • Binding Sites
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Crystallography, X-Ray
  • Escherichia coli / metabolism
  • Glycosylation
  • Glycosyltransferases / metabolism
  • Humans
  • Hydroxylation
  • Lysine / chemistry*
  • Markov Chains
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Elongation Factors / chemistry*
  • Peptides / chemistry
  • Phylogeny
  • Protein Biosynthesis
  • Pseudomonas aeruginosa / enzymology
  • RNA, Messenger / metabolism
  • Recombinant Proteins / chemistry
  • Rhamnose / chemistry*
  • Ribosomes / chemistry*
  • Shewanella / enzymology*
  • Tandem Mass Spectrometry


  • Peptide Elongation Factors
  • Peptides
  • RNA, Messenger
  • Recombinant Proteins
  • factor EF-P
  • Arginine
  • Glycosyltransferases
  • Lysine
  • Rhamnose