Atomic structure of progesterone complexed with its receptor

Shawn P. Williams and Paul B. Sigler ()
Additional contact information
Shawn P. Williams: Yale University
Paul B. Sigler: Yale University

Nature, 1998, vol. 393, issue 6683, 392-396

Abstract: Abstract The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily1. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals2. Here we report the 1.8 Å 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 receptors3,4,5,6, the progesterone receptor has a quite different mode of dimerization3,6. 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 repression7,8, 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.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/30775 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:393:y:1998:i:6683:d:10.1038_30775

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/30775

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().