Differential Role of Homologous Positively Charged Amino Acid Residues for Ligand Binding in Retinoic Acid Receptor α Compared with Retinoic Acid Receptor β
| Autor: | Kenneth J. Soprano, Jerome L. Gabriel, Dianne Robert Soprano, Christopher L. Wolfgang, Angela Scafonas |
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| Rok vydání: | 1997 |
| Předmět: |
Transcriptional Activation
Receptors Retinoic Acid medicine.drug_class Retinoic acid Tretinoin Retinoic acid receptor beta Biology Arginine Biochemistry Mice Retinoids chemistry.chemical_compound Transactivation medicine Animals Retinoid Vitamin A Receptor Molecular Biology Binding Sites Lysine Retinoic Acid Receptor alpha Amino Acids Diamino Stereoisomerism Cell Biology Retinoic acid receptor gamma Retinoic acid receptor chemistry Retinoic acid receptor alpha Mutation |
| Zdroj: | Journal of Biological Chemistry. 272:11244-11249 |
| ISSN: | 0021-9258 |
| Popis: | The diverse biological actions of retinoic acid (RA) are mediated by retinoic acid receptors (RARs) and retinoid X receptors. Although it has been suggested that the ligand binding domains (LBDs) of RARs share the same novel folding pattern, many RAR subtype-specific agonists and antagonists have been synthesized demonstrating that the LBD of each RAR subtype has unique features. We have examined the role of several positively charged amino acid residues located in the LBD of RARalpha in RA binding. These results are compared with previously published data for the homologous mutations in RARbeta. Lys227 of RARalpha does not appear to be important for RA binding or RA-dependent transactivation, whereas the homologous residue in RARbeta, Lys220, plays an important synergistic role with Arg269 in these two activities. In addition, Arg276 of RARalpha, like its homologous residue Arg269 of RARbeta, was found to play an important role in the binding of RA most likely by interacting with the carboxylate group of RA. However, the orientation of and electronic environment associated with Arg276 in RARalpha appears to be different from that of Arg269 in RARbeta, thus contributing to the uniqueness of the ligand binding pocket of each receptor. |
| Databáze: | OpenAIRE |
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