Atomic structure of progesterone complexed with its receptor

Nature. 1998 May 28;393(6683):392-6. doi: 10.1038/30775.


The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone-bound ligand-binding domain of the human progesterone receptor. The nature of this structure explains the receptor's selective affinity for progestins and establishes a common mode of recognition of 3-oxy steroids by the cognate receptors. Although the overall fold of the progesterone receptor is similar to that found in related receptors, the progesterone receptor has a quite different mode of dimerization. A hormone-induced stabilization of the carboxy-terminal secondary structure of the ligand-binding domain of the progesterone receptor accounts for the stereochemistry of this distinctive dimer, explains the receptor's characteristic pattern of ligand-dependent protease resistance and its loss of repression, and indicates how the anti-progestin RU486 might work in birth control. The structure also indicates that the analogous 3-keto-steroid receptors may have a similar mechanism of action.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Escherichia coli
  • Hormone Antagonists / pharmacology
  • Humans
  • Ligands
  • Mifepristone / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Progesterone / antagonists & inhibitors
  • Progesterone / chemistry*
  • Protein Conformation
  • Receptors, Progesterone / chemistry*
  • Recombinant Fusion Proteins / chemistry


  • Hormone Antagonists
  • Ligands
  • Receptors, Progesterone
  • Recombinant Fusion Proteins
  • Mifepristone
  • Progesterone

Associated data

  • PDB/1A28