title: A structural role for hormone in the thyroid hormone receptor.
abstract: 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.
authors.affiliation: Graduate Group in Biophysics, University of California at San Francisco 94143-0448, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Wagner
authors.forename: J W
authors.initials: JW
authors.lastname: Apriletti
authors.forename: M E
authors.initials: ME
authors.lastname: McGrath
authors.forename: B L
authors.initials: BL
authors.lastname: West
authors.forename: J D
authors.initials: JD
authors.lastname: Baxter
authors.forename: R J
authors.initials: RJ
authors.lastname: Fletterick
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013963:Thyroid Hormones / Q000819:agonists / Q000737:chemistry* / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D008024:Ligands; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D013963:Thyroid Hormones