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Solution structure of the glucocorticoid receptor DNA-binding domain
T Härd1, E Kellenbach, R Boelens
1Department of Chemistry, University of Utrecht, The Netherlands.
Summary
Researchers determined the 3D structure of the DNA-binding domain (DBD) of the glucocorticoid receptor using nuclear magnetic resonance. This reveals how the DBD interacts with DNA, crucial for gene regulation.
Area of Science:
- Structural biology
- Molecular biology
- Biochemistry
Background:
- The glucocorticoid receptor (GR) plays a vital role in gene regulation.
- Understanding the structure of its DNA-binding domain (DBD) is key to deciphering its function.
Purpose of the Study:
- To determine the three-dimensional structure of the DNA-binding domain (DBD) of the glucocorticoid receptor.
- To elucidate the structural basis for protein-DNA and protein-protein interactions.
Main Methods:
- Nuclear magnetic resonance (NMR) spectroscopy.
- Distance geometry calculations.
- Analysis of nuclear Overhauser enhancement (NOE) spectra.
Main Results:
- The 3D structure of a 71-residue protein fragment of the GR DBD was determined.
- The DBD comprises a globular body with extending finger regions, stabilized by two zinc atoms coordinated by cysteine residues.
- A model for the dimeric complex between the DBD and the glucocorticoid response element (GRE) was proposed.
Conclusions:
- The determined structure provides insights into the molecular mechanisms of glucocorticoid receptor function.
- The proposed model is consistent with known protein-DNA and protein-protein interactions involved in receptor binding to DNA.