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Related Experiment Videos

Gene regulation by the glucocorticoid receptor: structure:function relationship.

Raj Kumar1, E Brad Thompson

  • 1Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1068, USA.

The Journal of Steroid Biochemistry and Molecular Biology
|May 7, 2005
PubMed
Summary
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The glucocorticoid receptor (GR) structure, particularly its N-terminal domain, is largely unknown. Understanding its 3D structure is crucial for fully grasping GR functions and interactions.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Endocrinology

Background:

  • The glucocorticoid receptor (GR) is a key nuclear hormone receptor involved in gene regulation.
  • GR comprises N-terminal (NTD), DNA-binding (DBD), and ligand-binding (LBD) domains.
  • While DBD and LBD structures are known, the NTD and full-length GR structures remain elusive.

Purpose of the Study:

  • To review current knowledge on the structural aspects of the glucocorticoid receptor.
  • To discuss the functional implications of GR structure, including protein:DNA and protein:protein interactions.
  • To propose a model for GR action based on available structural and functional data.

Main Methods:

  • Literature review and synthesis of existing structural and functional data on the glucocorticoid receptor.

Related Experiment Videos

  • Analysis of factors influencing the conformation of the GR's N-terminal domain (NTD).
  • Development of a conceptual model for GR mechanism of action.

    • Main Results:

    • The NTD, containing the AF1 transactivation region, is often unstructured but can adopt specific conformations.
    • Conformational changes in the NTD are influenced by osmolytes, DNA binding (GRE), and protein-protein interactions.
    • Existing models do not fully explain all observed GR behaviors; a new model is proposed.

    Conclusions:

    • Knowledge of the full-length GR's three-dimensional structure is essential for understanding its functions.
    • The proposed model aims to better explain GR action, particularly concerning NTD conformational dynamics.
    • Structural principles of GR are likely applicable to other nuclear hormone receptors due to conserved organization.