Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.
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.
Fagart
Jérôme
J
INSERM U478, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, B.P. 416, 75870 Paris Cedex 18, France. fagart@bichat.inserm.fr
Huyet
Jessica
J
Pinon
Grégory M
GM
Rochel
Marina
M
Mayer
Claudine
C
Rafestin-Oblin
Marie-Edith
ME
D019943:Amino Acid Substitution; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008024:Ligands; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D018161:Receptors, Mineralocorticoid / Q000737:chemistry* / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry
D008024:Ligands; D018161:Receptors, Mineralocorticoid; D011994:Recombinant Proteins