Letter | Published:

Domain-specific recruitment of amide amino acids for protein synthesis

Nature volume 407, pages 106110 (07 September 2000) | Download Citation

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Abstract

The formation of aminoacyl-transfer RNA is a crucial step in ensuring the accuracy of protein synthesis. Despite the central importance of this process in all living organisms, it remains unknown how archaea and some bacteria synthesize Asn-tRNA and Gln-tRNA. These amide aminoacyl-tRNAs can be formed by the direct acylation of tRNA, catalysed by asparaginyl-tRNA synthetase and glutaminyl-tRNA synthetase, respectively. A separate, indirect pathway involves the formation of mis-acylated Asp-tRNAAsn or Glu-tRNA Gln, and the subsequent amidation of these amino acids while they are bound to tRNA, which is catalysed by amidotransferases1,2. Here we show that all archaea possess an archaea-specific heterodimeric amidotransferase (encoded by gatD and gatE) for Gln-tRNA formation. However, Asn-tRNA synthesis in archaea is divergent: some archaea use asparaginyl-tRNA synthetase, whereas others use a heterotrimeric amidotransferase (encoded by the gatA, gatB and gatC genes). Because bacteria primarily use transamidation3, and the eukaryal cytoplasm uses glutaminyl-tRNA synthetase, it appears that the three domains use different mechanisms for Gln-tRNA synthesis; as such, this is the only known step in protein synthesis where all three domains have diverged. Closer inspection of the two amidotransferases reveals that each of them recruited a metabolic enzyme to aid its function; this provides direct evidence for a relationship between amino-acid metabolism and protein biosynthesis.

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Acknowledgements

We thank R. Hedderich for M. thermoautotrophicum Marburg cells, J. Reeve for M. thermoautotrophicum ΔH DNA, K. O. Stetter for Pyrococcus cells, and H. Kobayashi for E. coli GlnRS and E. coli tRNAGln2 transcript. We also thank M. Ibba for critically reading the manuscript and S. Fitz-Gibbon, T. Hartsch, A. Johann, D. Oesterhelt, A. Ruepp and S. Schuster for sharing unpublished sequence data. D.L.T. and H.D.B. are postdoctoral fellows of the National Institute of General Medical Sciences and the EMBO, respectively. This work was supported by grants from the National Institute of General Medical Sciences.

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    • Debra L. Tumbula
    •  & Hubert D. Becker

    These authors contributed equally to this work

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  1. *Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA

    • Debra L. Tumbula
    • , Hubert D. Becker
    • , Wei-zhong Chang
    •  & Dieter Söll
  2. ‡Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA

    • Dieter Söll

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Correspondence to Dieter Söll.

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https://doi.org/10.1038/35024120

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