Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Structural basis for a degenerate tRNA identity code and the evolution of bimodal specificity in human mitochondrial tRNA recognition
Kuhle, B.; Hirschi, M.; Doerfel, L. K.; Lander, G. C. & Schimmel, P. (2023)
Nature Communications, 14(1). DOI: https://doi.org/10.1038/s41467-023-40354-2
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- Authors
- Kuhle, Bernhard; Hirschi, Marscha; Doerfel, Lili K.; Lander, Gabriel C.; Schimmel, Paul
- Abstract
- Abstract 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 Ser isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNA Ser(UGA) , and perform a structural and functional comparison with the mSerRS-mtRNA Ser(GCU) complex. We find that despite their common function, mtRNA Ser(UGA) and mtRNA Ser(GCU) 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 Ser . 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.
- Issue Date
- 2023
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English
- Sponsor
- U.S. Department of Health & Human Services | National Institutes of Health https://doi.org/10.13039/100000002
Damon Runyon Cancer Research Foundation https://doi.org/10.13039/100001021
Human Frontier Science Program https://doi.org/10.13039/501100000854
U.S. Department of Health & Human Services | National Institutes of Health
U.S. Department of Health & Human Services | National Institutes of Health
U.S. Department of Health & Human Services | National Institutes of Health
U.S. Department of Health & Human Services | National Institutes of Health
National Foundation for Cancer Research https://doi.org/10.13039/100001767
L. J. Skaggs and Mary C. Skaggs Foundation https://doi.org/10.13039/100003393