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Two crystal structures demonstrate large conformational changes in the eukaryotic ribosomal translocase

Nature Structural Biology volume 10, pages 379385 (2003) | Download Citation

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  • A Corrigendum to this article was published on 01 July 2003

Abstract

Two crystal structures of yeast translation elongation factor 2 (eEF2) were determined: the apo form at 2.9 Å resolution and eEF2 in the presence of the translocation inhibitor sordarin at 2.1 Å resolution. The overall conformation of apo eEF2 is similar to that of its prokaryotic homolog elongation factor G (EF-G) in complex with GDP. Upon sordarin binding, the three tRNA-mimicking C-terminal domains undergo substantial conformational changes, while the three N-terminal domains containing the nucleotide-binding site form an almost rigid unit. The conformation of eEF2 in complex with sordarin is entirely different from known conformations observed in crystal structures of EF-G or from cryo-EM studies of EF-G–70S complexes. The domain rearrangements induced by sordarin binding and the highly ordered drug-binding site observed in the eEF2–sordarin structure provide a high-resolution structural basis for the mechanism of sordarin inhibition. The two structures also emphasize the dynamic nature of the ribosomal translocase.

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Acknowledgements

We gratefully acknowledge access to the coordinates of eEF2-cryo (J. Frank) and the fitted coordinates of three states of EF-G (W. Wintermeyer). We also appreciate fruitful discussions with J. Nyborg. R.J. and G.R.A. were supported by Merck Research Laboratories, the Danish Science Research Council, Dansync and the EU. T.G.K. and P.A.O. were supported by the NIH. P.N., T.G.K. and G.R.A. were supported by the Human Frontiers Science Program.

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Affiliations

  1. Department of Molecular Biology, Aarhus University, Gustav Wieds vej 10C, DK8000 Århus, Denmark.

    • Rene Jørgensen
    • , Poul Nissen
    •  & Gregers Rom Andersen
  2. Department of Molecular Genetics, Microbiology and Immunology, UMDNJ Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

    • Pedro A. Ortiz
    • , Anne Carr-Schmid
    •  & Terri Goss Kinzy
  3. The Cancer Institute of New Jersey, Piscataway, New Jersey 08854, USA.

    • Terri Goss Kinzy

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The authors declare no competing financial interests.

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Correspondence to Gregers Rom Andersen.

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https://doi.org/10.1038/nsb923

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