Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.

The steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional...

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Main Authors: William H Hudson, Christine Youn, Eric A Ortlund
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0107000
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author William H Hudson
Christine Youn
Eric A Ortlund
author_facet William H Hudson
Christine Youn
Eric A Ortlund
author_sort William H Hudson
collection DOAJ
description The steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional structure shared among members of the steroid receptor family and their overlapping DNA binding preference, activation of individual steroid receptors drive unique effects on gene expression. Here, we present the first structure of the human mineralocorticoid receptor DNA binding domain, in complex with a canonical DNA response element. The overall structure is similar to the glucocorticoid receptor DNA binding domain, but small changes in the mode of DNA binding and lever arm conformation may begin to explain the differential effects on gene regulation by the mineralocorticoid and glucocorticoid receptors. In addition, we explore the structural effects of mineralocorticoid receptor DNA binding domain mutations found in type I pseudohypoaldosteronism and multiple types of cancer.
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publisher Public Library of Science (PLoS)
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series PLoS ONE
spelling doaj-art-7d0fe3c096ba42beb6ce99bbe4da3b262025-08-20T02:34:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10700010.1371/journal.pone.0107000Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.William H HudsonChristine YounEric A OrtlundThe steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional structure shared among members of the steroid receptor family and their overlapping DNA binding preference, activation of individual steroid receptors drive unique effects on gene expression. Here, we present the first structure of the human mineralocorticoid receptor DNA binding domain, in complex with a canonical DNA response element. The overall structure is similar to the glucocorticoid receptor DNA binding domain, but small changes in the mode of DNA binding and lever arm conformation may begin to explain the differential effects on gene regulation by the mineralocorticoid and glucocorticoid receptors. In addition, we explore the structural effects of mineralocorticoid receptor DNA binding domain mutations found in type I pseudohypoaldosteronism and multiple types of cancer.https://doi.org/10.1371/journal.pone.0107000
spellingShingle William H Hudson
Christine Youn
Eric A Ortlund
Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.
PLoS ONE
title Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.
title_full Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.
title_fullStr Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.
title_full_unstemmed Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.
title_short Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.
title_sort crystal structure of the mineralocorticoid receptor dna binding domain in complex with dna
url https://doi.org/10.1371/journal.pone.0107000
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AT christineyoun crystalstructureofthemineralocorticoidreceptordnabindingdomainincomplexwithdna
AT ericaortlund crystalstructureofthemineralocorticoidreceptordnabindingdomainincomplexwithdna