1
INSERM U478, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, B.P. 416, 75870 Paris Cedex 18, France.
2
Laboratoire de Recherche Moléculaire sur les Antibiotiques, INSERM U655, Université Paris 6, Faculté de Médecine Pitié-Salpêtrière, 91 boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
The S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension and switches progesterone from antagonist to agonist. Here we report the crystal structures of the ligand-binding domain of MR S810L in complex with progesterone and deoxycorticosterone, an agonist of both wild-type and mutant MRs. These structures, the first for MR, identify the specific contacts created by Leu810 and clarify the mechanism of activation of MR S810L.
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