Chimeric human mitochondrial PheRS exhibits editing activity to discriminate nonprotein amino acids

Ekaterine Kartvelishvili, Moshe Peretz, Dmitry Tworowski, Nina Moor, Mark Safro

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Mitochondria are considered as the primary source of reactive oxygen species (ROS) in nearly all eukaryotic cells during respiration. The harmful effects of these compounds range from direct neurotoxicity to incorporation into proteins producing aberrant molecules with multiple physiological problems. Phenylalanine exposure to ROS produces multiple oxidized isomers: tyrosine, Levodopa, ortho-Tyr, meta-Tyr (m-Tyr), and so on. Cytosolic phenylalanyl-tRNA synthetase (PheRS) exerts control over the translation accuracy, hydrolyzing misacylated products, while monomeric mitochondrial PheRS lacks the editing activity. Recently we showed that "teamwork" of cytosolic and mitochondrial PheRSs cannot prevent incorporation of m-Tyr and l-Dopa into proteins. Here, we present human mitochondrial chimeric PheRS with implanted editing module taken from EcPheRS. The monomeric mitochondrial chimera possesses editing activity, while in bacterial and cytosolic PheRSs this type of activity was detected for the (αβ)2 architecture only. The fusion protein catalyzes aminoacylation of tRNAPhe with cognate phenylalanine and effectively hydrolyzes the noncognate aminoacyl-tRNAs: Tyr-tRNAPhe and m-Tyr-tRNAPhe.

Original languageEnglish
Pages (from-to)618-626
Number of pages9
JournalProtein Science
Issue number3
StatePublished - Mar 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 The Protein Society.


FundersFunder number
NIH Office of the DirectorP40OD010440
National Institute of Neurological Disorders and StrokeR15NS081681


    • ROS-damaged amino acid
    • aminoacyl-tRNA synthetases
    • aminoacylation
    • chimera
    • editing
    • fusion protein


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