Download MendeleyThe peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading.
Gardner, B.M., Castanzo, D.T., Chowdhury, S., Stjepanovic, G., Stefely, M.S., Hurley, J.H., Lander, G.C., Martin, A.(2018) Nat Commun 9: 135-135
- PubMed: 29321502
- DOI: https://doi.org/10.1038/s41467-017-02474-4
- Primary Citation of Related Structures:
5VXV - PubMed 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.
Organizational Affiliation:
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720, USA.
