ArticleProceedings of the National Academy of Sciences of the United States of America2018
Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Membrane Protein Folding and Biogenesis: Insights from Single-Molecule Force Spectroscopy.Chemical reviews · 2026Review
- Look What You Made Me Do: Discerning Feature for Classification of Endocrine-Disrupting Chemical Binding to Steroid Hormone Receptors.Journal of chemical information and modeling · 2025Article
- Kindlin stabilizes the talin·integrin bond under mechanical load by generating an ideal bond.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Looking at Biomolecular Interactions through the Lens of Correlated Fluorescence Microscopy and Optical Tweezers.International journal of molecular sciences · 2023Review
- Rapid single-molecule characterisation of enzymes involved in nucleic-acid metabolism.Nucleic acids research · 2023Article
- Direct observation of chemo-mechanical coupling in DnaK by single-molecule force experiments.Biophysical journal · 2022Article
- Single-molecule mechanical studies of chaperones and their clients.Biophysics reviews · 2022Review
- Nucleic Acid Thermodynamics Derived from Mechanical Unzipping Experiments.Life (Basel, Switzerland) · 2022Review
- Active unfolding of the glucocorticoid receptor by the Hsp70/Hsp40 chaperone system in single-molecule mechanical experiments.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Article
- Co-Translational Folding of Multi-Domain Proteins.Frontiers in molecular biosciences · 2022Review
- Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network.Science advances · 2021Article
- Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis.Nanomaterials (Basel, Switzerland) · 2021Article
- Classifying Residues in Mechanically Stable and Unstable Substructures Based on a Protein Sequence: The Case Study of the DnaK Hsp70 Chaperone.Nanomaterials (Basel, Switzerland) · 2021Article
- Control of NanoscaleACS nano · 2021Article
- Sexual Dimorphism of Corticosteroid Signaling during Kidney Development.International journal of molecular sciences · 2021Review
- Studying protein folding in health and disease using biophysical approaches.Emerging topics in life sciences · 2021Article
- Modulation of a protein-folding landscape revealed by AFM-based force spectroscopy notwithstanding instrumental limitations.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A hierarchy of coupling free energies underlie the thermodynamic and functional architecture of protein structures.Current research in structural biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a "lid" structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of [Formula: see text] The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional [Formula: see text] of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s
Indexed as
Identifiers
What OpenQuestion holds
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.