Interaction of thyroid hormone nuclear receptor with antibody: characterization of the thyroid hormone binding site

Biochemical and Biophysical Research Communications
M K BhatS Y Cheng

Abstract

To understand the structural basis in the hormone-dependent transcriptional regulation of human beta 1 thyroid hormone receptor (h-TR beta 1), we characterized the region which interacted with the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3). Using the hormone binding domain of h-TR beta 1 (K206-D461) as an immunogen, we screened for monoclonal antibodies which inhibited the binding of T3 to h-TR beta 1. mAb C3, which recognized native h-TR beta 1, was obtained. Analyses of the binding data indicate that binding of T3 to h-TR beta 1 was competitively inhibited by mAb C3. Using a series of truncated mutants of h-TR beta 1 and synthetic peptides, we mapped the binding site of mAb C3 to the region of E248-V256. Thus, part of T3 binding site in h-TR beta 1 is in this nine-amino acid segment, which was shown by circular dichroism spectroscopy to be a random coil. Based on the proposed model of the hormone binding domain as an alpha/beta barrel, E248-V256 contains part of Loop 1 which is on the same side of the DNA binding domain. These results raise the possibility that Loop 1 could be in direct contact with the nearby DNA binding domain to affect the interaction of DNA binding domain with the T3 target genes.

Citations

Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·N YapS Y Cheng
Jun 5, 2013·Thyroid : Official Journal of the American Thyroid Association·Won Gu KimSheue-yann Cheng
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·A DaceS Cheng
Dec 14, 1995·Nature·R L WagnerR J Fletterick

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