Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension

Jérôme Fagart; Jessica Huyet; Grégory M. Pinon; Marina Rochel; Claudine Mayer; Marie Edith Rafestin-Oblin

doi:10.1038/nsmb939

Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension

Jérôme Fagart
, Jessica Huyet
, Grégory M. Pinon
, Marina Rochel
, Claudine Mayer
, Marie Edith Rafestin-Oblin

INSERM U869
AP-HP

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	554-555
Number of pages	2
Journal	Nature Structural and Molecular Biology
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/nsmb939
Publication status	Published - 1 Jan 2005
Externally published	Yes

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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.",

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AU - Fagart, Jérôme

AU - Huyet, Jessica

AU - Pinon, Grégory M.

AU - Rochel, Marina

AU - Mayer, Claudine

AU - Rafestin-Oblin, Marie Edith

PY - 2005/1/1

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N2 - 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.

AB - 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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DO - 10.1038/nsmb939

M3 - Article

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VL - 12

SP - 554

EP - 555

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

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ER -

Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension

Abstract

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