7TZB

Crystal structure of the human mitochondrial seryl-tRNA synthetase (mt SerRS) bound with a seryl-adenylate analogue

7TZB の概要

• エントリーDOI: 10.2210/pdb7tzb/pdb
• 分子名称: Serine--tRNA ligase, mitochondrial, 5'-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE (2 entities in total)
• 機能のキーワード: seryl-trna synthetase, mitochondria, aminoacylation, translation, trna, class ii, alpha-beta domain, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 109762.34

構造登録者

Kuhle, B.,Hirschi, M.,Doerfel, L.,Lander, G.,Schimmel, P. (登録日: 2022-02-15, 公開日: 2022-09-14, 最終更新日: 2023-10-18)

主引用文献

Kuhle, B.,Hirschi, M.,Doerfel, L.K.,Lander, G.C.,Schimmel, P.
Structural basis for shape-selective recognition and aminoacylation of a D-armless human mitochondrial tRNA.
Nat Commun, 13:5100-5100, 2022

PubMed Abstract: 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.

PubMed: 36042193
DOI: 10.1038/s41467-022-32544-1

実験手法

X-RAY DIFFRACTION (2.95 Å)