期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：9
页码：4028-4033
DOI：10.1073/pnas.1000315107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-tRNAThr 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.
关键词：aaRS ; quality control ; ROS ; translational fidelity
