Ligand-induced conformational changes in the mineralocorticoid receptor analyzed by protease mapping

Biochem Biophys Res Commun. 1995 Oct 4;215(1):286-91. doi: 10.1006/bbrc.1995.2464.


The human mineralocorticoid receptor (MR) binds the agonists aldosterone and cortisol and the antagonist progesterone with a comparably high affinity. We used limited proteolysis of human MR synthesized by in vitro translation to detect structural alterations induced by these different endogenous ligands. Steroid binding induces a conformational change within the receptor protein. This structural alteration renders a fragment of MR resistant 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 distinct conformational changes. Ligand-independent removal of MR-associated heat-shock proteins induces no detectable structural change but completely prevents ligand binding of MR.

MeSH terms

  • Aldosterone / metabolism*
  • Aldosterone / pharmacology
  • Chymotrypsin / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Hydrocortisone / metabolism*
  • Hydrocortisone / pharmacology
  • Mineralocorticoid Receptor Antagonists
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Mapping*
  • Progesterone / metabolism*
  • Progesterone / pharmacology
  • Protein Conformation / drug effects
  • Receptors, Mineralocorticoid / chemistry*
  • Receptors, Mineralocorticoid / metabolism
  • Subtilisins / metabolism
  • Trypsin / metabolism


  • Heat-Shock Proteins
  • Mineralocorticoid Receptor Antagonists
  • Peptide Fragments
  • Receptors, Mineralocorticoid
  • Aldosterone
  • Progesterone
  • Subtilisins
  • Chymotrypsin
  • Trypsin
  • Hydrocortisone