1a28
HORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAINHORMONE-BOUND HUMAN PROGESTERONE RECEPTOR LIGAND-BINDING DOMAIN
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Atomic structure of progesterone complexed with its receptor.,Williams SP, Sigler PB Nature. 1998 May 28;393(6683):392-6. PMID:9620806[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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