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A gated channel into the proteasome core particle

Nature Structural Biology volume 7, pages 1062–1067 (2000)Cite this article

Abstract

The core particle (CP) of the yeast proteasome is composed of four heptameric rings of subunits arranged in a hollow, barrel-like structure. We report that the CP is autoinhibited by the N-terminal tails of the outer (α) ring subunits. Crystallographic analysis showed that deletion of the tail of the α3-subunit opens a channel into the proteolytically active interior chamber of the CP, thus derepressing peptide hydrolysis. In the latent state of the particle, the tails prevent substrate entry by imposing topological closure on the CP. Inhibition by the α-subunit tails is relieved upon binding of the regulatory particle to the CP to form the proteasome holoenzyme.

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Figure 1: Deletion of the α3 tail opens a channel into the CP.
Figure 2: Electron density maps of the α ring of the yeast core particle from a, wild type and b, α3ΔN cells.
Figure 3: The α3ΔN core particle is constitutively activated for peptide hydrolysis.
Figure 4: Contacts among residues of the YDR element in adjacent tails.
Figure 5: Model for coupled regulation of proteasome assembly and inhibition.

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Acknowledgements

This work was supported by the NIH grant (to D.F.), the Foundation for the Promotion of Research at the Technion (M.H.G.), The US-Israel Binational Science Foundation (to M.H.G. and D.F.) and the Deutsche Forschungsgemeinschaft (to R.H.). A.K. was partially supported by a fellowship from the Studienfoerderung Cusanuswerk. The authors thank C. Larsen and G. Dittmar (Harvard) for generous assistance with computer imaging, K. Mann (Max-Planck-Institut für Biochemie, Martinsried, Germany) for help with N-terminal sequence analysis, and G. Bourenkow and H. Bartunik (DESY, Hamburg, Germany) for assistance with X-ray experiments.

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Author notes

  1. David M. Rubin

    Present address: Cognia, Inc., Mountain View, California, 94043, USA

  2. Monica Bajorek, Alwin Köhler, David M. Rubin and Daniel Finley: These authors contributed equally to this work.

Authors and Affiliations

  1. Max-Planck-Institut für Biochemie, Martinsried, D-82152, Germany

    Michael Groll, Luis Moroder & Robert Huber

  2. Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel

    Monica Bajorek & Michael H. Glickman

  3. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Alwin Köhler, David M. Rubin & Daniel Finley

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  1. Michael Groll
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Correspondence to Michael Groll, Michael H. Glickman or Daniel Finley.

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Groll, M., Bajorek, M., Köhler, A. et al. A gated channel into the proteasome core particle. Nat Struct Mol Biol 7, 1062–1067 (2000). https://doi.org/10.1038/80992

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