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

被引:3
|
作者
Kartvelishvili, Ekaterine [1 ]
Peretz, Moshe [1 ]
Tworowski, Dmitry [1 ]
Moor, Nina [2 ]
Safro, Mark [1 ]
机构
[1] Weizmann Inst Sci, Dept Biol Struct, Hertzel Str, IL-76100 Rehovot, Israel
[2] Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia
关键词
chimera; aminoacyl-tRNA synthetases; ROS-damaged amino acid; fusion protein; aminoacylation; editing; TRANSFER-RNA-SYNTHETASE; THERMUS-THERMOPHILUS; CRYSTAL-STRUCTURE; GENE ENCODES; TYROSINE; MISINCORPORATION; SIMULATION; MECHANISM; TRNA(PHE); CATALYZE;
D O I
10.1002/pro.2855
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 ()(2) architecture only. The fusion protein catalyzes aminoacylation of tRNA(Phe) with cognate phenylalanine and effectively hydrolyzes the noncognate aminoacyl-tRNAs: Tyr-tRNA(Phe) and m-Tyr-tRNA(Phe).
引用
收藏
页码:618 / 626
页数:9
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