AAA peroxins and their recruiter Pex26p modulate the interactions of peroxins involved in peroxisomal protein import

J Biol Chem. 2014 Aug 29;289(35):24336-46. doi: 10.1074/jbc.M114.588038. Epub 2014 Jul 11.

Abstract

Pex1p and Pex6p are required for the relocation of the import receptor Pex5p from the peroxisomal membrane to the cytosol. We herein show that mammalian Pex26p directly binds to Pex14p, the initial docking receptor of Pex5p, and interacts with Pex5p via Pex14p. The binding affinity of Pex26p to Pex14p is altered by Pex5p. Further evidence suggests that the N-terminal region in Pex26p acts as a scaffold protein to recruit Pex14p·Pex5p complex together with Pex1p·Pex6p complexes on peroxisomes. Pex26p binding to Pex14p was suppressed by overexpression of Pex1p and Pex6p in an ATP-dependent manner, whereas Pex14p was not competed out by Pex1p and Pex6p from Pex26p mutant defective in peroxisomal matrix protein import. These results suggested that peroxisome biogenesis requires Pex1p- and Pex6p-regulated dissociation of Pex14p from Pex26p. Pex1p homo-oligomer directly binds to Pex5p as assessed by a surface plasmon resonance-based assay. Moreover, cytosolic Pex1p is likely to maintain the functional oligomer of Pex5p. Taken together, in the peroxisomal protein import, AAA peroxins modulate the interaction between Pex26p and Pex14p on peroxisome membrane as well as Pex5p oligomer in the cytosol.

Keywords: AAA Peroxins; ATPase; Peroxisome; Pex14p; Pex26p; Protein Complex; Protein Import; Protein Targeting; Scaffold Protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / physiology*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Base Sequence
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • DNA Primers
  • HEK293 Cells
  • Humans
  • Membrane Proteins / physiology*
  • Native Polyacrylamide Gel Electrophoresis
  • Polymerase Chain Reaction
  • Protein Binding

Substances

  • DNA Primers
  • Membrane Proteins
  • PEX26 protein, human
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, human
  • PEX6 protein, human