Ligand-binding and heterodimerization activities of a conserved region in the ligand-binding domain of the thyroid hormone receptor.
The ligand-binding domain of the thyroid hormone (3,5,3'-triiodothyronine) receptor (TR) contains poorly characterized subdomains involved with ligand binding, transactivation, and protein-protein interactions. The region between residues 288-331 of rat TR alpha-1 was analyzed by modeling and site-directed mutagenesis. Our results suggest that part of this sequence adopts an amphipathic alpha-helical conformation. The integrity of the putative helix is important for 3,5,3'-triiodothyronine binding but not necessarily for heterodimerization with nuclear factor(s). Mutants defective for both activities were found clustered in a region overlapping the C-terminal portion of the helix and further downstream. The sequence conservation of this particular region among the entire superfamily suggests a similar role in dimerization in other receptors.
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
R A
RA
Spanjaard
D S
DS
Darling
W W
WW
Chin
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004252:DNA Mutational Analysis; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D051381:Rats; D011987:Receptors, Steroid / Q000737:chemistry; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000648:ultrastructure; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000378:metabolism
D008024:Ligands; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine