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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0107000 |
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| _version_ | 1850124821069824000 |
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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. |
| format | Article |
| id | doaj-art-7d0fe3c096ba42beb6ce99bbe4da3b26 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| 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 |
| work_keys_str_mv | AT williamhhudson crystalstructureofthemineralocorticoidreceptordnabindingdomainincomplexwithdna AT christineyoun crystalstructureofthemineralocorticoidreceptordnabindingdomainincomplexwithdna AT ericaortlund crystalstructureofthemineralocorticoidreceptordnabindingdomainincomplexwithdna |