title: Conformational changes in chicken thyroid hormone receptor alpha 1 induced by binding to ligand or to DNA.
abstract: A classic model of steroid/thyroid hormone receptor activation postulates that a conformational change or "transformation" occurs upon ligand binding as a first step toward regulation of gene transcription. In order to test this model, physical studies have been carried out using purified full-length chicken thyroid hormone receptor alpha 1 (cT3R-alpha 1) expressed in Escherichia coli. Circular dichroism spectroscopic studies reveal that cT3R-alpha 1 adopts a different conformation upon specific binding to a cognate ligand triiodothyroacetic acid as well as to a thyroid hormone response element, an idealized inverted repeat AGGTCA TGACCT. These results suggest that cT3R-alpha 1 may adopt distinct conformations whether free or bound to ligand or to DNA. These states may reflect the changes in the conformation of steroid/thyroid hormone receptors in the signal transduction pathway.
authors.affiliation: Department of Molecular Pharmacology and Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
authors.forename: J H
authors.initials: JH
authors.lastname: Toney
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: A E
authors.initials: AE
authors.lastname: Summerfield
authors.forename: G
authors.initials: G
authors.lastname: Sanyal
authors.forename: B M
authors.initials: BM
authors.lastname: Forman
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: H H
authors.initials: HH
authors.lastname: Samuels
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002645:Chickens; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli; D006358:Hot Temperature; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014284:Triiodothyronine; D004247:DNA