title: Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.
abstract: 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.
authors.affiliation: INSERM U478, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, B.P. 416, 75870 Paris Cedex 18, France. fagart@bichat.inserm.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Fagart
authors.forename: Jessica
authors.initials: J
authors.lastname: Huyet
authors.forename: Grégory M
authors.initials: GM
authors.lastname: Pinon
authors.forename: Marina
authors.initials: M
authors.lastname: Rochel
authors.forename: Claudine
authors.initials: C
authors.lastname: Mayer
authors.forename: Marie-Edith
authors.initials: ME
authors.lastname: Rafestin-Oblin
mesh_terms: 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
chemical_list: D008024:Ligands; D018161:Receptors, Mineralocorticoid; D011994:Recombinant Proteins