| abstract |
An isolated mineralocorticoid receptor (MR) polypeptide, or functional portion thereof, having one or more mutations that alter the solubility or crystal-forming properties and confer the ability to generate soluble protein complexes with the MR and ligands that only weakly bind the native polypeptide, and a polynucleotide encoding it are disclosed. Representative mutations are C808S and S810L substitutions. Expression of the MR polypeptide in E. coli is also provided. A solved three-dimensional crystal structure of an MR ligand binding domain polypeptide is also disclosed, along with a crystalline form of the MR ligand binding domain polypeptide. Methods of modeling one or more molecular interactions of a native NR with a ligand having low affinity for the native NR utilizing a mutated MR, designing modulators of the biological activity of MR and other nuclear receptor, steroid receptor and glucocorticoid receptor polypeptides and nuclear receptor, steroid receptor and glucocorticoid receptor ligand binding domain polypeptides are also disclosed. |