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TitleStructure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 5942, Year 2023
Publish dateSep 23, 2023
AuthorsMaximilian Rüttermann / Michelle Koci / Pascal Lill / Ermis Dionysios Geladas / Farnusch Kaschani / Björn Udo Klink / Ralf Erdmann / Christos Gatsogiannis /
PubMed AbstractThe double-ring AAA+ ATPase Pex1/Pex6 is required for peroxisomal receptor recycling and is essential for peroxisome formation. Pex1/Pex6 mutations cause severe peroxisome associated developmental ...The double-ring AAA+ ATPase Pex1/Pex6 is required for peroxisomal receptor recycling and is essential for peroxisome formation. Pex1/Pex6 mutations cause severe peroxisome associated developmental disorders. Despite its pathophysiological importance, mechanistic details of the heterohexamer are not yet available. Here, we report cryoEM structures of Pex1/Pex6 from Saccharomyces cerevisiae, with an endogenous protein substrate trapped in the central pore of the catalytically active second ring (D2). Pairs of Pex1/Pex6(D2) subdomains engage the substrate via a staircase of pore-1 loops with distinct properties. The first ring (D1) is catalytically inactive but undergoes significant conformational changes resulting in alternate widening and narrowing of its pore. These events are fueled by ATP hydrolysis in the D2 ring and disengagement of a "twin-seam" Pex1/Pex6(D2) heterodimer from the staircase. Mechanical forces are propagated in a unique manner along Pex1/Pex6 interfaces that are not available in homo-oligomeric AAA-ATPases. Our structural analysis reveals the mechanisms of how Pex1 and Pex6 coordinate to achieve substrate translocation.
External linksNat Commun / PubMed:37741838 / PubMed Central
MethodsEM (single particle)
Resolution4.1 - 4.7 Å
Structure data

EMDB-16372, PDB-8c0v:
Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate in single seam state
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-16373, PDB-8c0w:
Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate in twin seam state
Method: EM (single particle) / Resolution: 4.7 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsTRANSLOCASE / AAA ATPase / peroxisomes / peroxisome biogenesis / peroxisome biogenesis disorders / Zellweger Syndrome

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