1A28

HORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAIN

Summary for 1A28

• Entry DOI: 10.2210/pdb1a28/pdb
• Descriptor: PROGESTERONE RECEPTOR, PROGESTERONE (3 entities in total)
• Functional Keywords: progesterone receptor, steroid receptor, nuclear receptor, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus. Isoform A: Nucleus: P06401
• Total number of polymer chains: 2
• Total formula weight: 59738.19

Authors

Sigler, P.B.,Williams, S.P. (deposition date: 1998-01-19, release date: 1998-07-15, Last modification date: 2024-02-07)

Primary citation

Williams, S.P.,Sigler, P.B.
Atomic structure of progesterone complexed with its receptor.
Nature, 393:392-396, 1998

PubMed Abstract: 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.

PubMed: 9620806
DOI: 10.1038/30775

Experimental method

X-RAY DIFFRACTION (1.8 Å)