Arg278, but not Lys229 or Lys236, plays an important role in the binding of retinoic acid by retinoic acid receptor γ

Zhen Ping Zhang, Carlo J. Gambone, Jerome L. Gabriel, Christopher L. Wolfgang, Kenneth J. Soprano, Dianne Robert Soprano

Research output: Contribution to journalArticlepeer-review


The diverse biological actions of retinoic acid (RA) are mediated by retinoic acid receptors (RARα, β and γ) and retinoid X receptors (RXR α, β, and γ). Although the ligand-binding domains of RARs share the same novel folding pattern, many RAR subtype-specific retinoids have been synthesized indicating that the ligand-binding pocket of each RAR subtype has unique features. Previously we have demonstrated the importance for HA binding and RA-dependent transactivation of Arg276 of RARα alone and in RARβ Arg269 in conjunction with Lys220. In this study, we have examined the role of the homologous amino acid residues (Lys229 and Arg278) in RARγ for these activities. Like RARα but dissimilar to RARβ Arg278 in RARγ alone was found to play an important role in RA binding and RA-dependent transactivation. Since Lys236 in RARγ was suggested from the crystal structure of holo-RARγ, to interact with RA, we also examined its role and that of its homologs in RARα and RARβ. Despite the suggestion from the crystal structure, neither Lys236 nor its homologs in RARα and RARβ play a role in the binding of RA or RA-dependent transactivation. It is likely that Lys236 in RARγ and its homologs in RARα and RARβ are solvent exposed rather than pointing into the RA-binding pocket.

Original languageEnglish (US)
Pages (from-to)34016-34021
Number of pages6
JournalJournal of Biological Chemistry
Issue number51
StatePublished - Dec 18 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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