7TZB

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

Summary for 7TZB

• Entry DOI: 10.2210/pdb7tzb/pdb
• Descriptor: Serine--tRNA ligase, mitochondrial, 5'-O-(N-(L-SERYL)-SULFAMOYL)ADENOSINE (2 entities in total)
• Functional Keywords: seryl-trna synthetase, mitochondria, aminoacylation, translation, trna, class ii, alpha-beta domain, ligase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 109762.34

Authors

Kuhle, B.,Hirschi, M.,Doerfel, L.,Lander, G.,Schimmel, P. (deposition date: 2022-02-15, release date: 2022-09-14, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.95 Å)