Retinoid X Receptor Alters the Determination of DNA Binding Specificity by the P-box Amino Acids of the Thyroid Hormone Receptor
| Autor: | Jonathan S. Faris, Paul J. Romaniuk, Stephen C. Hendy, Colleen C. Nelson |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Protein Folding
Receptors Retinoic Acid Base pair Molecular Sequence Data Biology Biochemistry Biopolymers Humans Amino Acid Sequence Amino Acids Molecular Biology Hormone response element Binding Sites Receptors Thyroid Hormone Thyroid hormone receptor Base Sequence Retinoid X receptor alpha DNA Cell Biology DNA-binding domain Retinoid X receptor gamma DNA-Binding Proteins Retinoid X Receptors Nuclear receptor Retinoid X receptor beta Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 271:19464-19474 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.32.19464 |
| Popis: | Nuclear hormone receptors bind to hormone response elements in DNA consisting of two half-sites of 6 base pairs. The P-box amino acids of each receptor determine the identities of the central nucleotides of the half-site. 57 P-box variants of the human thyroid hormone receptor (hT3Rbeta) were used to demonstrate the relationship between P-box sequence and DNA binding specificity by homodimers and heterodimers formed with the retinoid X receptor (RXR). In general, the formation of heterodimers relieved many of the constraints on the compatibility of hT3Rbeta P-box sequences with DNA binding. Effects were most dramatic for heterodimers bound to a direct repeat spaced by four base pairs. RXR also overrides the P-box-derived DNA binding specificity of hT3Rbeta when heterodimers are bound to inverted or everted repeat elements. These effects of RXR are most pronounced on AGGTCA half-sites but are squelched when the RXR partner of the heterodimer is bound to an AGGACA half-site. The influence of RXR on hT3Rbeta DNA binding specificity varies with the orientation of half-sites in the element, the identity of the fourth base pair of the half-site, and the spacing between the half-sites of direct repeats. These differences suggest that the DNA binding domains of RXR-hT3Rbeta heterodimers are not positioned equivalently on the various elements, affecting the manner in which the P-box amino acids of hT3Rbeta interact with base pairs within the half-site. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|