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

• DOI: 10.1038/s41467-017-02474-4
• Publication Date: 2018-01-03T23:01:51Z
• Authors: Brooke M. Gardner; Dominic T. Castanzo; Saikat Chowdhury; Goran Stjepanovic; Matthew S. Stefely; James H. Hurley; Gabriel C. Lander; Andreas Martin
• Keywords: AAA proteins; Zellweger syndrome

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