The Pex1/Pex6 complex is a heterohexameric AAA+ motor with alternating and highly coordinated subunits

J Mol Biol. 2015 Mar 27;427(6 Pt B):1375-1388. doi: 10.1016/j.jmb.2015.01.019. Epub 2015 Feb 7.


Pex1 and Pex6 are Type-2 AAA+ ATPases required for the de novo biogenesis of peroxisomes. Mutations in Pex1 and Pex6 account for the majority of the most severe forms of peroxisome biogenesis disorders in humans. Here, we show that the ATP-dependent complex of Pex1 and Pex6 from Saccharomyces cerevisiae is a heterohexamer with alternating subunits. Within the Pex1/Pex6 complex, only the D2 ATPase ring hydrolyzes ATP, while nucleotide binding in the D1 ring promotes complex assembly. ATP hydrolysis by Pex1 is highly coordinated with that of Pex6. Furthermore, Pex15, the membrane anchor required for Pex1/Pex6 recruitment to peroxisomes, inhibits the ATP-hydrolysis activity of Pex1/Pex6.

Keywords: AAA+ ATPase; Pex1; Pex15; Pex6; peroxisome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Hydrolysis
  • Image Processing, Computer-Assisted
  • Immunoprecipitation
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Microscopy, Electron
  • Models, Molecular
  • Molecular Sequence Data
  • Peroxisomes / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Conformation
  • Protein Multimerization
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid


  • Membrane Proteins
  • PEX15 protein, S cerevisiae
  • Phosphoproteins
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, S cerevisiae
  • PEX6 protein, S cerevisiae