LIGAND-INDUCED CONFORMATIONAL-CHANGES IN THE MINERALOCORTICOID RECEPTOR ANALYZED BY PROTEASE MAPPING

The human mineralocorticoid receptor (MR) binds the agonists aldostero ne and cortisol and the antagonist progesterone with a comparably high affinity. We used limited proteolysis of human MR synthesized by in v itro translation to detect structural alterations induced by these dif ferent endogenous ligands, Steroid binding induces a conformational ch ange within the receptor protein. This structural alteration renders a fragment of MR resistent to proteolysis. Agonists and antagonist vary in how well they protect the MR fragment against proteolysis. But the two agonists also differ in their ability to protect, indicating that agonists and antagonists, but also different agonists, may induce dis tinct conformational changes. Ligand-independent removal of MR-associa ted heat-shock proteins induces no detectable structural change but co mpletely prevents ligand binding of MR. (C) 1995 Academic Press. Inc.