ArticleMolecular biology of the cell2010
Biological and structural basis for Aha1 regulation of Hsp90 ATPase activity in maintaining proteostasis in the human disease cystic fibrosis.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
98 citing papers in PubMed, 168 citations in OpenAlex.
- Antifungal metallacarboranes modulate Hsp90 activity.Future medicinal chemistry · 2026Article
- Hsp90: A means to an end.Cell stress & chaperones · 2026Review
- Distinct phosphorylation mechanisms as dynamic switches for Hsp90 regulation.Nature communications · 2026Article
- Collaboration between two conserved sequence motifs drives ATPase stimulation of Hsp90 by Aha1.Protein science : a publication of the Protein Society · 2025Article
- Hsp90 and associates shaping parasite biology.mSphere · 2025Review
- Benzbromarone interferes with the interaction between Hsp90 and Aha1 by interacting with both of them.Communications biology · 2025Article
- The known unknowns of the Hsp90 chaperone.eLife · 2024Review
- Evolution of the conformational dynamics of the molecular chaperone Hsp90.Nature communications · 2024Article
- Optimization of the fluorogen-activating protein tag for quantitative protein trafficking and colocalization studies inMolecular biology of the cell · 2024Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- The role of Aha1 in cancer and neurodegeneration.Frontiers in molecular neuroscience · 2024Review
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Aha1 regulates Hsp90's conformation and function in a stoichiometry-dependent way.Biophysical journal · 2023Article
- Nucleotide exchange is sufficient for Hsp90 functions in vivo.Nature communications · 2023Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Article
- UBBAging · 2021Article
- The interactions of molecular chaperones with client proteins: why are they so weak?The Journal of biological chemistry · 2021Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The activator of Hsp90 ATPase 1, Aha1, has been shown to participate in the Hsp90 chaperone cycle by stimulating the low intrinsic ATPase activity of Hsp90. To elucidate the structural basis for ATPase stimulation of human Hsp90 by human Aha1, we have developed novel mass spectrometry approaches that demonstrate that the N- and C-terminal domains of Aha1 cooperatively bind across the dimer interface of Hsp90 to modulate the ATP hydrolysis cycle and client activity in vivo. Mutations in both the N- and C-terminal domains of Aha1 impair its ability to bind Hsp90 and stimulate its ATPase activity in vitro and impair in vivo the ability of the Hsp90 system to modulate the folding and trafficking of wild-type and variant (DeltaF508) cystic fibrosis transmembrane conductance regulator (CFTR) responsible for the inherited disease cystic fibrosis (CF). We now propose a general model for the role of Aha1 in the Hsp90 ATPase cycle in proteostasis whereby Aha1 regulates the dwell time of Hsp90 with client. We suggest that Aha1 activity integrates chaperone function with client folding energetics by modulating ATPase sensitive N-terminal dimer structural transitions, thereby protecting transient folding intermediates in vivo that could contribute to protein misfolding systems disorders such as CF when destabilized.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.