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Complete subunit architecture of the proteasome regulatory particle

Author

Listed:
  • Gabriel C. Lander

    (Lawrence Berkeley National Laboratory, University of California)

  • Eric Estrin

    (University of California)

  • Mary E. Matyskiela

    (University of California)

  • Charlene Bashore

    (University of California)

  • Eva Nogales

    (Lawrence Berkeley National Laboratory, University of California
    Howard Hughes Medical Institute, University of California
    QB3 Institute, University of California)

  • Andreas Martin

    (University of California
    QB3 Institute, University of California)

Abstract

The proteasome is the major ATP-dependent protease in eukaryotic cells, but limited structural information restricts a mechanistic understanding of its activities. The proteasome regulatory particle, consisting of the lid and base subcomplexes, recognizes and processes polyubiquitinated substrates. Here we used electron microscopy and a new heterologous expression system for the lid to delineate the complete subunit architecture of the regulatory particle from yeast. Our studies reveal the spatial arrangement of ubiquitin receptors, deubiquitinating enzymes and the protein unfolding machinery at subnanometre resolution, outlining the substrate’s path to degradation. Unexpectedly, the ATPase subunits within the base unfoldase are arranged in a spiral staircase, providing insight into potential mechanisms for substrate translocation through the central pore. Large conformational rearrangements of the lid upon holoenzyme formation suggest allosteric regulation of deubiquitination. We provide a structural basis for the ability of the proteasome to degrade a diverse set of substrates and thus regulate vital cellular processes.

Suggested Citation

  • Gabriel C. Lander & Eric Estrin & Mary E. Matyskiela & Charlene Bashore & Eva Nogales & Andreas Martin, 2012. "Complete subunit architecture of the proteasome regulatory particle," Nature, Nature, vol. 482(7384), pages 186-191, February.
    • Handle: RePEc:nat:nature:v:482:y:2012:i:7384:d:10.1038_nature10774
    DOI: 10.1038/nature10774
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    Cited by:

    1. Nathan Jespersen & Kai Ehrenbolger & Rahel R. Winiger & Dennis Svedberg & Charles R. Vossbrinck & Jonas Barandun, 2022. "Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Toshihiko Ogura, 2012. "High-Contrast Observation of Unstained Proteins and Viruses by Scanning Electron Microscopy," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-7, October.

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