Related Experiment Video
Updated: Aug 11, 2025
11:07
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
16.5K
Quaternary glucocorticoid receptor structure highlights allosteric interdomain communication
Sandra Postel1, Lisa Wissler1, Carina A Johansson1
1Mechanistic & Structural Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden.
Nature Structural & Molecular Biology
|February 7, 2023
Summary
Glucocorticoid receptor (GR) structures reveal its asymmetric dimer formation on DNA. Ligand binding transmits signals across GR domains, offering insights for drug design in inflammatory diseases.
Area of Science:
- Structural biology
- Molecular pharmacology
- Genetics
Background:
- Glucocorticoid receptor (GR) is a key transcription factor targeted by agonists for inflammatory and autoimmune diseases.
- Understanding GR's structural dynamics is crucial for optimizing therapeutic strategies.
Purpose of the Study:
- To elucidate the high-resolution, multidomain structures of GR bound to ligand, DNA, and co-regulator peptides.
- To reveal the mechanism of asymmetric dimer formation and inter-domain communication within GR.
Main Methods:
- High-resolution structural analysis (crystallography or cryo-EM implied).
- Hydrogen-deuterium exchange mass spectrometry (HDX-MS).
- DNA-binding assays.
Main Results:
- Detailed structures of GR in complex with ligand, DNA, and co-regulator peptide were determined.
- GR forms an asymmetric dimer on DNA, with specific inter-monomer domain interactions observed.
- Ligand-dependent structural changes are effectively communicated across all domains of the full-length GR.
Conclusions:
- GR adopts a unique architectural conformation on DNA.
- Ligand pharmacophore modulates GR signal transmission, impacting gene regulation.
- Findings provide a foundation for understanding GR modifications in disease and designing novel therapeutics.
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