A structural role for hormone in the thyroid hormone receptor

Nature. 1995 Dec 14;378(6558):690-7. doi: 10.1038/378690a0.


The crystal structure of the rat alpha 1 thyroid hormone receptor ligand-binding domain bound with a thyroid hormone agonist reveals that ligand is completely buried within the domain as part of the hydrophobic core. In addition, the carboxy-terminal activation domain forms an amphipathic helix, with its hydrophobic face constituting part of the hormone binding cavity. These observations suggest a structural role for ligand, in establishing the active conformation of the receptor, that is likely to underlie hormonal regulation of gene expression for the nuclear receptors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Computer Graphics
  • Crystallography, X-Ray
  • Escherichia coli
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Rats
  • Receptors, Thyroid Hormone / chemistry*
  • Receptors, Thyroid Hormone / physiology
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Thyroid Hormones / agonists
  • Thyroid Hormones / chemistry*
  • Thyroid Hormones / physiology
  • Transcriptional Activation


  • Ligands
  • Receptors, Thyroid Hormone
  • Recombinant Proteins
  • Thyroid Hormones