39] Glucocorticoid receptor thiols andsteroid-binding activity

Abstract

The amino acids that determine the steroid-binding sites of steroid receptors are located in the COOH-terminal in a region referred to as the “horome-binding domain” (HBD). An additional determinant for steroid-binding activity of the glucocorticoid receptor (GR) is the presence or absence of an intramolecular disulfide between a vicinally spaced pair of cysteine SH groups lying in the HBD. The studies of the redox manipulation of cytosolic steroid-binding activity have focused on the glucocorticoid receptor and, when the primary structure of this receptor was determined, it became clear that the GR contains a unique bithiol in the HBD. With the advent of molecular biology techniques, precise investigations on the role of thiols in steroid binding have become possible. This chapter summarizes the evolution of current thinking on how thiols influence the ligand-binding properties of glucocorticoid receptors.