ArticleProceedings of the National Academy of Sciences of the United States of America2022
Active unfolding of the glucocorticoid receptor by the Hsp70/Hsp40 chaperone system in single-molecule mechanical experiments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Glucocorticoid Receptor Signaling in Myeloid Cells Orchestrates Inflammation Resolution and Muscle Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Corticosteroids in asthma and COPD: an inflammopharmacological perspective on molecular and genetic determinants.Molecular biology reports · 2026Review
- The timing of antenatal glucocorticoids determines the receptor sensitivity in preterm infants.The Journal of clinical endocrinology and metabolism · 2026Article
- Single-Chain Studies Reveal that Neutral Poly(2-ethyl-2-oxazoline) Exhibits Polyelectrolyte-like Behavior in Aqueous Solutions.Polymer science & technology (Washington, D.C.) · 2026Article
- ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors.The Biochemical journal · 2026Review
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Mechanisms of assembly and function of the Hsp70-Hsp40 chaperone machinery.Molecular cell · 2025Article
- Glucocorticoid Insensitivity: Is It a Question of Time and Place?Biomedicines · 2025Review
- Single-molecule study of the dynamics of the molecular chaperone Hsp70 during the functional cycle.Biochemical Society transactions · 2025Review
- Hsp90: Bringing it all together.Cell stress & chaperones · 2025Review
- Chaperone-mediated disaggregation of infectious prions releases particles that seed new prion formation in a strain-specific manner.The Journal of biological chemistry · 2025Article
- The known unknowns of the Hsp90 chaperone.eLife · 2024Review
- Ectoin attenuates cortisone-induced skin issues by suppression GR signaling and the UVB-induced overexpression of 11β-HSD1.Journal of cosmetic dermatology · 2024Article
- Force-regulated chaperone activity of BiP/ERdj3 is opposite to their homologs DnaK/DnaJ.Protein science : a publication of the Protein Society · 2024Article
- Tandem repeats of highly bioluminescent NanoLuc are refolded noncanonically by the Hsp70 machinery.Protein science : a publication of the Protein Society · 2024Article
- Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.Cellular and molecular life sciences : CMLS · 2023Article
- Human Small Heat Shock Protein B8 Inhibits Protein Aggregation without Affecting the Native Folding Process.Journal of the American Chemical Society · 2023Article
- Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins.eLife · 2023Article
- Looking at Biomolecular Interactions through the Lens of Correlated Fluorescence Microscopy and Optical Tweezers.International journal of molecular sciences · 2023Review
- Single-molecule mechanical studies of chaperones and their clients.Biophysics reviews · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glucocorticoid receptor (GR) is an important transcription factor and drug target linked to a variety of biological functions and diseases. It is one of the most stringent physiological clients of the Hsp90/Hsp70/Hsp40 chaperone system. In this study, we used single-molecule force spectroscopy by optical tweezers to observe the interaction of the GR’s ligand-binding domain (GR-LBD) with the Hsp70/Hsp40 chaperone system (Hsp70/40). We show in real time that Hsp70/40 can unfold the complete GR-LBD in a stepwise manner. Each unfolding step involves binding of an Hsp70 to the GR-LBD and subsequent adenosine triphosphate (ATP) hydrolysis, stimulated by Hsp40. The kinetics of chaperone-mediated unfolding depend on chaperone concentrations as well as the presence of the nucleotide exchange factor BAG1. We find that Hsp70/40 can stabilize new unfolding intermediates, showing that Hsp70/40 can directly interact with the folded core of the protein when working as an unfoldase. Our results support an unfolding mechanism where Hsp70 can directly bind to folded protein structures and unfold them upon ATP hydrolysis. These results provide important insights into the regulation of GR by Hsp70/40.
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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.