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

Lassak, J., Keilhauer, E. C., Fürst, M., Wuichet, K., Gödeke, J., Starosta, A. L., Chen, J-M., Søgaard-Andersen, L., Rohr, J., Wilson, D. N., Häussler, S., Mann, M. & Jung, K., 16-Feb-2015, In : Nature Chemical Biology.

Research output: Contribution to journalArticleAcademicpeer-review

  • Jürgen Lassak
  • Eva C Keilhauer
  • Maximilian Fürst
  • Kristin Wuichet
  • Julia Gödeke
  • Agata L Starosta
  • Jhong-Min Chen
  • Lotte Søgaard-Andersen
  • Jürgen Rohr
  • Daniel N Wilson
  • Susanne Häussler
  • Matthias Mann
  • Kirsten Jung

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.

Original languageEnglish
JournalNature Chemical Biology
Publication statusPublished - 16-Feb-2015
Externally publishedYes

ID: 16903742