Atomic structure of progesterone complexed with its receptor.
Williams, Shawn P.; Sigler, Paul B.
[Letter] Nature. 393(6683):392-396, May 28, 1998.

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The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily [1].As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals [2]. Here we report the 1.8 Angstrom 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 [3-6], the progesterone receptor has a quite different mode of dimerization [3,6]. A hormone-induced stabilization of the carboxy-terminal secondary structure of the ligand-binding domain of the progesterone receptor accounts for the stereo-chemistry of this distinctive dimer, explains the receptor's characteristic pattern of ligand-dependent protease resistance and its loss of repression [7,8], 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.

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