Document Type
Article
Publication Date
9-28-2021
Abstract
High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNAPhe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNAPhe, despite these oxidized residues not being directly implicated in PheRS activity. Here, we solve a 3.6 Å cryo-electron microscopy structure of oxidized S. Typhimurium PheRS. We find that oxidation results in widespread structural rearrangements in the β-subunit editing domain and enlargement of its editing domain. Oxidization also enlarges the phenylalanyl-adenylate binding pocket but to a lesser extent. Together, these changes likely explain why oxidation leads to hyperaccurate editing and decreased misincorporation of tyrosine. Taken together, these results help increase our understanding of the survival of S. Typhimurium during human infection.
Recommended Citation
Pooja Srinivas, Rebecca E Steiner, Ian J Pavelich, Ricardo Guerrero-Ferreira, Puneet Juneja, Michael Ibba, Christine M Dunham, Oxidation alters the architecture of the phenylalanyl-tRNA synthetase editing domain to confer hyperaccuracy, Nucleic Acids Research, 2021;, gkab856, https://doi.org/10.1093/nar/gkab856
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
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Comments
This article was originally published in Nucleic Acids Researchin 2021. https://doi.org/10.1093/nar/gkab856