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Related Experiment Videos

A structural role for hormone in the thyroid hormone receptor

R L Wagner1, J W Apriletti, M E McGrath

  • 1Graduate Group in Biophysics, University of California at San Francisco 94143-0448, USA.

Nature
|December 14, 1995
PubMed
Summary

Thyroid hormone agonists bind within the hydrophobic core of the rat alpha 1 thyroid hormone receptor. This structural interaction suggests a role for the ligand in establishing the receptor's active conformation for gene regulation.

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Patents and literature.

Applied biochemistry and biotechnology·2013

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Nuclear receptors, including thyroid hormone receptors, play crucial roles in regulating gene expression.
  • Understanding the structural basis of ligand-receptor interactions is key to deciphering hormonal signaling pathways.

Purpose of the Study:

  • To elucidate the crystal structure of the rat alpha 1 thyroid hormone receptor ligand-binding domain complexed with a thyroid hormone agonist.
  • To investigate the structural role of the ligand in receptor conformation and function.

Main Methods:

  • X-ray crystallography was employed to determine the high-resolution crystal structure of the receptor-ligand complex.
  • Structural analysis focused on the ligand-binding domain and the carboxy-terminal activation domain.

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Main Results:

  • The thyroid hormone agonist was found to be completely buried within the hydrophobic core of the ligand-binding domain.
  • The carboxy-terminal activation domain formed an amphipathic helix, with its hydrophobic face contributing to the hormone-binding cavity.

Conclusions:

  • Ligand binding is integral to the hydrophobic core, suggesting a structural role in stabilizing the receptor's active conformation.
  • These findings provide insights into the mechanism of hormonal regulation of gene expression mediated by nuclear receptors.