Serine-tRNA ligase, type1 / Serine-tRNA ligase catalytic core domain / Serine-tRNA synthetase, type1, N-terminal domain superfamily / Class I and II aminoacyl-tRNA synthetase, tRNA-binding arm / Aminoacyl-tRNA synthetase, class II (G/ P/ S/T) / tRNA synthetase class II core domain (G, H, P, S and T) / Aminoacyl-tRNA synthetase, class II / Aminoacyl-transfer RNA synthetases class-II family profile. / Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL) 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM125908
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
AG067594
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
AG061697
米国
National Institutes of Health/Office of the Director
S10OD021634
米国
引用
ジャーナル: Nat Commun / 年: 2023 タイトル: Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition. 著者: Bernhard Kuhle / Marscha Hirschi / Lili K Doerfel / Gabriel C Lander / Paul Schimmel / 要旨: Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic ...Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic interplay between strong mutation pressure on mtRNAs and selection pressure to maintain their essential function. To understand the molecular consequences of this interplay, we analyze the human mitochondrial serylation system, in which one synthetase charges two highly divergent mtRNA isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNA, and perform a structural and functional comparison with the mSerRS-mtRNA complex. We find that despite their common function, mtRNA and mtRNA show no constrain to converge on shared structural or sequence identity motifs for recognition by mSerRS. Instead, mSerRS evolved a bimodal readout mechanism, whereby a single protein surface recognizes degenerate identity features specific to each mtRNA. Our results show how the mutational erosion of mtRNAs drove a remarkable innovation of intermolecular specificity rules, with multiple evolutionary pathways leading to functionally equivalent outcomes.