| Leucine at codon 428 in the ninth heptad of thyroid hormone receptor beta1 is necessary for interactions with the transcriptional cofactors and functions regardless of dimer formations. | |
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MedLine Citation:
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PMID: 12855009 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Structure/function studies of the thyroid hormone receptor (TR) beta(1) have demonstrated that single amino acid substitutions in either position 428 or 429 in the ligand-binding domain (LBD) can alter heterodimerizations and homodimerizations, respectively. A leucine at 428 is located in a highly conserved region corresponding to the putative ninth heptad repeat of a leucine-zipper-like motif in the LBD of TRbeta(1). To investigate how the side chain of amino acids at 428 affect receptor characteristics, gel-shift mobility shift assays and yeast two-hybrid assays were analyzed. The neutral status amino acids such as a leucine (wild-type) or a glutamine at 428 preferred heterodimerization with RXR. Furthermore, a positively charged side chain of amino acids at 428 such as an arginine or a lysine, preserved homodimer formation. Irrespective of charge, ninth heptad mutant receptors did not bind the ligand and were not able to interact with either corepressor or coactivating proteins. Limited trypsinization assays revealed no major conformational change in the ninth heptad mutant receptors. Together, these findings suggested that a leucine at 428 was a critical amino acid for both interaction with the thyroid hormone receptor associated proteins and ligand-independent and -dependent functions regardless of dimer formations. |
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Authors:
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Tsuyoshi Monden; Masanobu Yamada; Sumiyasu Ishii; Takeshi Hosoya; Teturo Satoh; Fredric E Wondisford; Anthony N Hollenberg; Masatomo Mori |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Thyroid : official journal of the American Thyroid Association Volume: 13 ISSN: 1050-7256 ISO Abbreviation: Thyroid Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-07-11 Completed Date: 2004-03-26 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9104317 Medline TA: Thyroid Country: United States |
Other Details:
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Languages: eng Pagination: 427-35 Citation Subset: IM |
Affiliation:
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First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan. tmonden@showa.gunma-u.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Amino Acids / chemistry, genetics Animals Cell Line Cercopithecus aethiops Codon / genetics* Dimerization Electrophoretic Mobility Shift Assay Leucine / chemistry, genetics* Nuclear Proteins / chemistry, metabolism Nuclear Receptor Co-Repressor 1 Protein Conformation Receptors, Retinoic Acid / chemistry, metabolism Recombinant Proteins / chemistry, genetics, metabolism Repressor Proteins / metabolism Response Elements / genetics Retinoid X Receptors Saccharomyces cerevisiae / genetics Thyroid Hormone Receptors beta / chemistry, genetics*, metabolism* Transcription Factors / chemistry, metabolism* Transfection Two-Hybrid System Techniques |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Codon; 0/Nuclear Proteins; 0/Nuclear Receptor Co-Repressor 1; 0/Receptors, Retinoic Acid; 0/Recombinant Proteins; 0/Repressor Proteins; 0/Retinoid X Receptors; 0/Thyroid Hormone Receptors beta; 0/Transcription Factors; 61-90-5/Leucine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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