title: Molecular snapshots of the Pex1/6 AAA+ complex in action.
abstract: The peroxisomal proteins Pex1 and Pex6 form a heterohexameric type II AAA+ ATPase complex, which fuels essential protein transport across peroxisomal membranes. Mutations in either ATPase in humans can lead to severe peroxisomal disorders and early death. We present an extensive structural and biochemical analysis of the yeast Pex1/6 complex. The heterohexamer forms a trimer of Pex1/6 dimers with a triangular geometry that is atypical for AAA+ complexes. While the C-terminal nucleotide-binding domains (D2) of Pex6 constitute the main ATPase activity of the complex, both D2 harbour essential substrate-binding motifs. ATP hydrolysis results in a pumping motion of the complex, suggesting that Pex1/6 function involves substrate translocation through its central channel. Mutation of the Walker B motif in one D2 domain leads to ATP hydrolysis in the neighbouring domain, giving structural insights into inter-domain communication of these unique heterohexameric AAA+ assemblies.
authors.affiliation: Gene Center Munich, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, Munich 81377, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ciniawsky
authors.affiliation: Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr-Universität Bochum, Bochum 44801, Germany.
authors.forename: Immanuel
authors.initials: I
authors.lastname: Grimm
authors.affiliation: Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr-Universität Bochum, Bochum 44801, Germany.
authors.forename: Delia
authors.initials: D
authors.lastname: Saffian
authors.affiliation: Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr-Universität Bochum, Bochum 44801, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Girzalsky
authors.affiliation: Institute of Biochemistry and Pathobiochemistry, Department of Systems Biochemistry, Faculty of Medicine, Ruhr-Universität Bochum, Bochum 44801, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Erdmann
authors.affiliation: Gene Center Munich, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, Munich 81377, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Wendler
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D019281:Dimerization; D006868:Hydrolysis; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C511586:PEX1 protein, S cerevisiae; C490760:PEX6 protein, S cerevisiae