The unfolded protein response (UPR) is a conserved homeostatic program that is activated by misfolded proteins in the lumen of the endoplasmic reticulum (ER). Recently, it became evident that aberrant lipid compositions of the ER membrane, referred to as lipid bilayer stress, are equally potent in activating the UPR. The underlying molecular mechanism, however, remained unclear. We show that the most conserved transducer of ER stress, Ire1, uses an amphipathic helix (AH) to sense membrane aberrancies and control UPR activity. In vivo and in vitro experiments, together with molecular dynamics (MD) simulations, identify the physicochemical properties of the membrane environment that control Ire1 oligomerization. This work establishes the molecular mechanism of UPR activation by lipid bilayer stress.
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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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