Identification of sulfhydryl-modified cysteine residues in the ligand binding pocket of retinoic acid receptor β

Christopher L. Wolfgang, Zhen Ping Zhang, Jerome L. Gabriele, Ronald A. Pieringer, Kenneth J. Soprano, Dianne Robert Soprano

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The diverse biological functions of retinoic acid (RA) are mediated through retinoic acid receptors (RARs) and retinoid X receptors. HAHs contain a high affinity binding site for RA which is sensitive to treatment with sulfhydryl modification reagents. In an attempt to identify which Cys residues are important for this loss of binding, we created three site- specific RARβ mutants: C228A, C258A, and C267A. The affinity for RA of all three mutant receptors was in the range of that of the wild type protein, suggesting that none of these Cys residues are critical for RA binding. Rather, these modified Cys residue(s) function to sterically hinder RA binding; however, the modified Cys residues critical for the inhibition of binding differ depending on the reagent employed. Only modification of Cys228 is necessary to inhibit RA binding when RARβ is modified by reagents which transfer large bulky groups while both Cys228 and Cys267 must be modified when a small functional group is transferred. These data suggest that both Cys228 and Cys267 but not Cys258 lie in the ligand binding pocket of RARβ. However, Cys228 lies closer to the opening of the RARβ ligand binding pocket whereas Cys267 lies more deeply buried.

Original languageEnglish (US)
Pages (from-to)746-753
Number of pages8
JournalJournal of Biological Chemistry
Issue number2
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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