A structural role for hormone in the thyroid hormone receptor.
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.
Wagner
R L
RL
Graduate Group in Biophysics, University of California at San Francisco 94143-0448, USA.
Apriletti
J W
JW
McGrath
M E
ME
West
B L
BL
Baxter
J D
JD
Fletterick
R J
RJ
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
D008024:Ligands; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D013963:Thyroid Hormones