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 on Aging (NIH/NIA)
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: 2022 タイトル: Structural basis for shape-selective recognition and aminoacylation of a D-armless human mitochondrial tRNA. 著者: Bernhard Kuhle / Marscha Hirschi / Lili K Doerfel / Gabriel C Lander / Paul Schimmel / 要旨: Human mitochondrial gene expression relies on the specific recognition and aminoacylation of mitochondrial tRNAs (mtRNAs) by nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs). ...Human mitochondrial gene expression relies on the specific recognition and aminoacylation of mitochondrial tRNAs (mtRNAs) by nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs). Despite their essential role in cellular energy homeostasis, strong mutation pressure and genetic drift have led to an unparalleled sequence erosion of animal mtRNAs. The structural and functional consequences of this erosion are not understood. Here, we present cryo-EM structures of the human mitochondrial seryl-tRNA synthetase (mSerRS) in complex with mtRNA. These structures reveal a unique mechanism of substrate recognition and aminoacylation. The mtRNA is highly degenerated, having lost the entire D-arm, tertiary core, and stable L-shaped fold that define canonical tRNAs. Instead, mtRNA evolved unique structural innovations, including a radically altered T-arm topology that serves as critical identity determinant in an unusual shape-selective readout mechanism by mSerRS. Our results provide a molecular framework to understand the principles of mito-nuclear co-evolution and specialized mechanisms of tRNA recognition in mammalian mitochondrial gene expression.