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Structural insight into the role of the ribosomal tunnel in cellular regulation

Nature Structural & Molecular Biology volume 10, pages 366–370 (2003)Cite this article

Abstract

Nascent proteins emerge out of ribosomes through an exit tunnel, which was assumed to be a firmly built passive path. Recent biochemical results, however, indicate that the tunnel plays an active role in sequence-specific gating of nascent chains and in responding to cellular signals. Consistently, modulation of the tunnel shape, caused by the binding of the semi-synthetic macrolide troleandomycin to the large ribosomal subunit from Deinococcus radiodurans, was revealed crystallographically. The results provide insights into the tunnel dynamics at high resolution. Here we show that, in addition to the typical steric blockage of the ribosomal tunnel by macrolides, troleandomycin induces a conformational rearrangement in a wall constituent, protein L22, flipping the tip of its highly conserved β-hairpin across the tunnel. On the basis of mutations that alleviate elongation arrest, the tunnel motion could be correlated with sequence discrimination and gating, suggesting that specific arrest motifs within nascent chain sequences may induce a similar gating mechanism.

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Figure 1: The binding mode of TAO to the large ribosomal subunit.
Figure 2: The global conformational changes of L22 hairpin triggered by TAO binding.
Figure 3: The putative progression of SecM arrest in the exit tunnel.

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Acknowledgements

We thank G. Glaser, R. Zarivach and P. Fucini for critical discussions; I. Agmon, R. Albrecht, C. Liebe, A. Wolff, H. Bartels, W.S. Bennett, E. Ben-Zeev, C. Glotz, H.A.S. Hansen, M. Kessler and A. McLeod for participating in this work; and the staff at ID19/SBC/APS and ID29/ESRF/EMBL. The Max-Planck-Society, the US National Institutes of Health, the German Science & Technology Ministry and the Kimmelman Center for Macromolecular Assembly provided support. A.Y. holds the Hellen and Martin Kimmel Professorial Chair.

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Authors and Affiliations

  1. Max-Planck-Research Unit for Ribosomal Structure, Hamburg, Germany

    Rita Berisio, Frank Schluenzen, Joerg Harms & Ada Yonath

  2. Institute of Biostructure and Bioimaging, CNR, Napoli, Italy

    Rita Berisio

  3. Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel

    Anat Bashan, Tamar Auerbach, David Baram & Ada Yonath

  4. Institute of Biochemistry, the Free University, Berlin, Germany

    Tamar Auerbach

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Correspondence to Ada Yonath.

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Berisio, R., Schluenzen, F., Harms, J. et al. Structural insight into the role of the ribosomal tunnel in cellular regulation. Nat Struct Mol Biol 10, 366–370 (2003). https://doi.org/10.1038/nsb915

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