The molecular chaperone heat-shock protein 90 (Hsp90) couples ATP hydrolysis to conformational changes driving a reaction cycle that is required for substrate activation. Recent structural analysis provided snapshots of the open and closed states of Hsp90, which mark the starting and end points of these changes. Using fluorescence resonance energy transfer (FRET), we dissected the cycle kinetically and identified the intermediates on the pathway. The conformational transitions are orders of magnitude slower than the ATP-hydrolysis step and thus are the limiting events during the reaction cycle. Furthermore, these structural changes can be tightly regulated by cochaperones, being completely inhibited by Sti1 or accelerated by Aha1. In fact, even in the absence of nucleotide, Aha1 induces Hsp90 rearrangements that speed up the conformational cycle. This comprehensive reconstitution of the Hsp90 cycle defines a controlled progression through distinct intermediates that can be modulated by conformation-sensitive cochaperones.
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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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