• Media type: E-Article
  • Title: Severe oxidative stress induces protein mistranslation through impairment of an aminoacyl-tRNA synthetase editing site
  • Contributor: Ling, Jiqiang; Söll, Dieter
  • Published: Proceedings of the National Academy of Sciences, 2010
  • Published in: Proceedings of the National Academy of Sciences, 107 (2010) 9, Seite 4028-4033
  • Language: English
  • DOI: 10.1073/pnas.1000315107
  • ISSN: 0027-8424; 1091-6490
  • Origination:
  • Footnote:
  • Description: Oxidative stress arises from excessive reactive oxygen species (ROS) and affects organisms of all three domains of life. Here we present a previously unknown pathway through which ROS may impact faithful protein synthesis. Aminoacyl-tRNA synthetases are key enzymes in the translation of the genetic code; they attach the correct amino acid to each tRNA species and hydrolyze an incorrectly attached amino acid in a process called editing. We show both in vitro and in vivo in Escherichia coli that ROS reduced the overall translational fidelity by impairing the editing activity of threonyl-tRNA synthetase. Hydrogen peroxide oxidized cysteine182 residue critical for editing, leading to Ser-tRNA Thr formation and protein mistranslation that impaired growth of Escherichia coli . The presence of major heat shock proteases was required to allow cell growth in medium containing serine and hydrogen peroxide; this suggests that the mistranslated proteins were misfolded.
  • Access State: Open Access