Two membrane-bound ATP-dependent AAA proteases conduct protein quality surveillance in the inner membrane of mitochondria and control crucial steps during mitochondrial biogenesis. AAA domains of proteolytic subunits are critical for the recognition of non-native membrane proteins which are extracted from the membrane bilayer for proteolysis. Here, we have analysed the role of the conserved loop motif YVG, which has been localized to the central pore in other hexameric AAA(+) ring complexes, for the degradation of membrane proteins by the i-AAA protease Yme1. Proteolytic activity was found to depend on the presence of hydrophobic amino acid residues at position 354 within the pore loop of Yme1. Mutations affected proteolysis in a substrate-specific manner: whereas the degradation of misfolded membrane proteins was impaired at a post-binding step, folded substrate proteins did not interact with mutant Yme1. This reflects most likely deficiencies in the ATP-dependent unfolding of substrate proteins, since we observed similar effects for ATPase-deficient Yme1 mutants. Our findings therefore suggest an essential function of the central pore loop for the ATP-dependent translocation of membrane proteins into a proteolytic cavity formed by AAA proteases.
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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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