Protein-protein interactions between the DNA-binding domains of nuclear receptors: influence on DNA-binding.
The glucocorticoid and thyroid hormone receptors have the capacity to bind as dimers to palindromic DNA-binding sites. Protein-protein interactions between the DNA-binding domains of glucocorticoid receptor dimers restrict the DNA-binding to elements where the half-sites are separated by three base pairs, whereas DNA-binding by the thyroid hormone receptor does not appear to require a strict half-site spacing. We have previously shown that a five amino-acid segment close the the C-terminal zinc-binding site (D-box) was involved in dimerization of the glucocorticoid receptor (GR) DNA-binding domain (Dahlman-Wright et al., 1991, J. Biol. Chem., 266, 3107-3112). Here we provide functional evidence, using mutated thyroid hormone receptor DNA-binding domains, that this five amino acid segment (D-box) of the GR interacts with the equivalent segment on the second DNA-binding domain in the dimer. In contrast, the thyroid hormone receptor DNA-binding domain binds to palindromic thyroid hormone response elements in a weakly co-operative manner, independent of the D-box.
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Sweden.
K
K
Dahlman-Wright
K
K
Grandien
S
S
Nilsson
J A
JA
Gustafsson
J
J
Carlstedt-Duke
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013205:Staphylococcal Protein A
D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D004247:DNA