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Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway

Author

Listed:
  • Ian Cooney

    (University of Utah)

  • Heidi L. Schubert

    (University of Utah)

  • Karina Cedeno

    (University of Utah)

  • Olivia N. Fisher

    (University of Utah)

  • Richard Carson

    (Brigham Young University)

  • John C. Price

    (Brigham Young University)

  • Christopher P. Hill

    (University of Utah)

  • Peter S. Shen

    (University of Utah)

Abstract

The Cdc48 AAA+ ATPase is an abundant and essential enzyme that unfolds substrates in multiple protein quality control pathways. The enzyme includes two conserved AAA+ ATPase motor domains, D1 and D2, that assemble as hexameric rings with D1 stacked above D2. Here, we report an ensemble of native structures of Cdc48 affinity purified from budding yeast lysate in complex with the adaptor Shp1 in the act of unfolding substrate. Our analysis reveals a continuum of structural snapshots that spans the entire translocation cycle. These data uncover elements of Shp1-Cdc48 interactions and support a ‘hand-over-hand’ mechanism in which the sequential movement of individual subunits is closely coordinated. D1 hydrolyzes ATP and disengages from substrate prior to D2, while D2 rebinds ATP and re-engages with substrate prior to D1, thereby explaining the dominant role played by the D2 motor in substrate translocation/unfolding.

Suggested Citation

  • Ian Cooney & Heidi L. Schubert & Karina Cedeno & Olivia N. Fisher & Richard Carson & John C. Price & Christopher P. Hill & Peter S. Shen, 2024. "Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51835-3
    DOI: 10.1038/s41467-024-51835-3
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    References listed on IDEAS

    as
    1. Yang Xu & Han Han & Ian Cooney & Yuxuan Guo & Noah G. Moran & Nathan R. Zuniga & John C. Price & Christopher P. Hill & Peter S. Shen, 2022. "Active conformation of the p97-p47 unfoldase complex," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
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