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The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading

Author

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  • Brooke M. Gardner

    (University of California, Berkeley)

  • Dominic T. Castanzo

    (University of California, Berkeley)

  • Saikat Chowdhury

    (The Scripps Research Institute)

  • Goran Stjepanovic

    (University of California, Berkeley
    Lawrence Berkeley National Laboratory)

  • Matthew S. Stefely

    (University of California, Berkeley)

  • James H. Hurley

    (University of California, Berkeley
    Lawrence Berkeley National Laboratory
    University of California, Berkeley)

  • Gabriel C. Lander

    (The Scripps Research Institute)

  • Andreas Martin

    (University of California, Berkeley
    University of California, Berkeley
    University of California, Berkeley)

Abstract

Pex1 and Pex6 form a heterohexameric motor essential for peroxisome biogenesis and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis disorders in humans. The tail-anchored protein Pex15 recruits Pex1/Pex6 to the peroxisomal membrane, where it performs an unknown function required for matrix-protein import. Here we determine that Pex1/Pex6 from S. cerevisiae is a protein translocase that unfolds Pex15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Our structural studies of Pex15 in isolation and in complex with Pex1/Pex6 illustrate that Pex15 binds the N-terminal domains of Pex6, before its C-terminal disordered region engages with the pore loops of the motor, which then processively threads Pex15 through the central pore. Furthermore, Pex15 directly binds the cargo receptor Pex5, linking Pex1/Pex6 to other components of the peroxisomal import machinery. Our results thus support a role of Pex1/Pex6 in mechanical unfolding of peroxins or their extraction from the peroxisomal membrane during matrix-protein import.

Suggested Citation

  • Brooke M. Gardner & Dominic T. Castanzo & Saikat Chowdhury & Goran Stjepanovic & Matthew S. Stefely & James H. Hurley & Gabriel C. Lander & Andreas Martin, 2018. "The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02474-4
    DOI: 10.1038/s41467-017-02474-4
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    Cited by:

    1. Maximilian Rüttermann & Michelle Koci & Pascal Lill & Ermis Dionysios Geladas & Farnusch Kaschani & Björn Udo Klink & Ralf Erdmann & Christos Gatsogiannis, 2023. "Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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