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Related Experiment Videos

Structure and function of the glucocorticoid receptor

A P Wright1, J Zilliacus, I J McEwan

  • 1Center for Biotechnology, Karolinska Institute, Huddinge, Sweden.

The Journal of Steroid Biochemistry and Molecular Biology
|December 1, 1993
PubMed
Summary

Glucocorticoid receptor (GR) activation involves hormone binding, dimerization, and DNA interaction to regulate gene expression. Structural and genetic studies reveal key roles for specific GR domains in these processes.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Glucocorticoids regulate gene expression through the intracellular glucocorticoid receptor (GR).
  • GR function involves hormone binding, dimerization, DNA binding, and gene expression modulation.
  • Understanding GR's multi-step signaling is crucial for deciphering its biological roles.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying glucocorticoid receptor (GR) function.
  • To investigate the roles of different GR domains in hormone binding, dimerization, and DNA interaction.
  • To identify specific amino acids critical for GR DNA-binding specificity and transcriptional activation.

Main Methods:

  • Tertiary structure determination of the GR.
  • Biochemical assays to assess GR activity.

Related Experiment Videos

  • Genetic screening in yeast to identify functional GR mutants.
  • Squelching experiments to study protein-protein interactions.

    • Main Results:

    • GR dimerization and high-affinity DNA binding depend on contacts involving both DNA and steroid-binding domains.
    • Specific amino acids in the GR DNA-binding domain's recognition helix dictate binding specificity for hormone response elements.
    • The N-terminal transactivation domain interacts with general transcriptional machinery distinct from TFIID.

    Conclusions:

    • GR function is a multi-step process involving distinct structural and functional domains.
    • Structural and genetic insights reveal the molecular basis for GR's specific DNA recognition and transcriptional control.
    • GR interacts with general transcription factors beyond TFIID for gene activation.