Valine 571 functions as a regional organizer in programming the glucocorticoid receptor for differential binding of glucocorticoids and mineralocorticoids.

摘要: The glucocorticoid receptor (GR) interacts specifically with glucocorticoids, whereas its closest relative, the mineralocorticoid (MR), both glucocorticoids and mineralocorticoids, such as aldosterone. To investigate mechanism underlying glucocorticoid/mineralocorticoid specificity of GR, we used a yeast model system to screen for GR ligand-binding domain mutants, substituted MR residues in segment 565-574, that can be efficiently activated by In all increased activity valine 571 was replaced methionine, even though most mutants also contained substitutions other their counterparts. Further analysis COS-7 cells has revealed identity residue determines behavior 565-574 segment. Generally, this region are only consistent aldosterone binding if is methionine (MR conformation). If (GR conformation), substitution drastically reduce interaction hormones. Based on these functional data, hypothesize functions regional organizer involved discriminating between We have molecular an attempt interpret our data structural terms.