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Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.

Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin ME

INSERM U478, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, B.P. 416, 75870 Paris Cedex 18, France. fagart@bichat.inserm.fr

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.

Published 3 June 2005 in Nat Struct Mol Biol, 12(6): 554-5.
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