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Structures of the human and Drosophila 80S ribosome

Nature volume 497, pages 80–85 (2013)Cite this article

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Abstract

Protein synthesis in all cells is carried out by macromolecular machines called ribosomes. Although the structures of prokaryotic, yeast and protist ribosomes have been determined, the more complex molecular architecture of metazoan 80S ribosomes has so far remained elusive. Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. These structures not only illustrate the co-evolution of metazoan-specific ribosomal RNA with ribosomal proteins but also reveal the presence of two additional structural layers in metazoan ribosomes, a well-ordered inner layer covered by a flexible RNA outer layer. The human and Drosophila ribosome structures will provide the basis for more detailed structural, biochemical and genetic experiments.

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Figure 1: Structures of the human and Drosophila 80S ribosomes.
Figure 2: Protein architecture of the human 80S ribosome and associated factors.
Figure 3: Metazoan rRNA expansion segments.
Figure 4: Dynamic behaviour and co-evolution of expansion segments.
Figure 5: Layered evolution of the eukaryotic ribosome.

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Protein Data Bank

Data deposits

Coordinates of the atomic models have been deposited in the Protein Data Bank with accession numbers 3J38, 3J39, 3J3C and 3J3E for Drosophila 80S ribosomes and 3J3A, 3J3B, 3J3D and 3J3F for human 80S ribosomes. Full models can be obtained from the database of aligned ribosomal complexes (DARC) site (http://darcsite.genzentrum.lmu.de/darc/). Electron-microscopy maps of the Drosophila and human ribosomes have been deposited in the EM Data Bank under the accession codes EMD-5591 and EMD-5592, respectively. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests. Readers are welcome to comment on the online version of the paper. Correspondence and requests for materials should be addressed to R.B. (beckmann@lmb.uni-muenchen.de).

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Acknowledgements

We thank C. Ungewickell for assistance with cryo-EM data collection and P. Palluch for preparation of peripheral blood mononucleic cells. We thank M. Yusupov, A. Ben-Shem, N. Garreau de Loubresse and S. Melnikov for sharing S. cerevisiae X-ray data before publication. We thank P. Becker for access to his fly facility and help with embryo collection, and V. Márquez, T. Fröhlich, G. Arnold, I. Forné and A. Imhof for mass-spectrometry analysis. This research was supported by grants from the Deutsche Forschungsgemeinschaft SFB594, SFB646 and GRK 1721 (to R.B.), and FOR1805 (to R.B. and D.N.W.). D.N.W. is supported by the European Molecular Biology Organization (EMBO) young investigator program. This work was supported by a European Research Council (ERC) Advanced Grant (to R.B.).

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  1. Andreas M. Anger and Jean-Paul Armache: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Center for integrated Protein Science Munich (CiPSM), Gene Center, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377, Munich, Germany

    Andreas M. Anger, Jean-Paul Armache, Otto Berninghausen, Daniel N. Wilson & Roland Beckmann

  2. Department of Empirical Inference, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany,

    Michael Habeck

  3. Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 38, 72076 Tübingen, Germany,

    Michael Habeck

  4. Department of Internal Medicine III, Klinikum der Universität München and Clinical Cooperation Group Immunotherapy at the Helmholtz Institute Munich, Marchioninistrasse 15, 81377 Munich, Germany,

    Marion Subklewe

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Contributions

A.M.A. prepared D. melanogaster embryo extracts, purified D. melanogaster and H. sapiens ribosome samples, carried out mass-spectrometry analysis of H. sapiens ribosomes and prepared the figures; A.M.A. and J.-P.A. contributed blood, processed cryo-EM data and built atomic models; O.B. carried out cryo-EM data collection; M.H. performed deconvolution and sharpening on electron density maps; M.S. designed experiments for blood collection and peripheral-blood-mononuclear-cell preparations for human ribosome purification; A.M.A., J.-P.A., D.N.W. and R.B. interpreted results and wrote the manuscript. D.N.W. and R.B. designed research and supervised the project.

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Correspondence to Roland Beckmann.

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Anger, A., Armache, JP., Berninghausen, O. et al. Structures of the human and Drosophila 80S ribosome. Nature 497, 80–85 (2013). https://doi.org/10.1038/nature12104

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