PEX1 and PEX6 form a heterohexameric motor essential for peroxisome biogenesis and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis disorders in humans. The tail-anchored protein PEX15 recruits PEX1/PEX6 to the peroxisomal membrane, where it performs an unknown function required for matrix-protein import. Here we determine that PEX1/PEX6 from S. cerevisiae is a protein translocase that unfolds PEX15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Our structural studies of PEX15 in isolation and in complex with PEX1/PEX6 illustrate that PEX15 binds the N-terminal domains of PEX6, before its C-terminal disordered region engages with the pore loops of the motor, which then processively threads PEX15 through the central pore. Furthermore, PEX15 directly binds the cargo receptor PEX5, linking PEX1/PEX6 to other components of the peroxisomal import machinery. Our results thus support a role of PEX1/PEX6 in mechanical unfolding of peroxins or their extraction from the peroxisomal membrane during matrix-protein import.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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