Crystal Structure of the Mineralocorticoid Receptor DNA Binding Domain in Complex with DNA

Hudson, William H.; Youn, Christine; Ortlund, Eric A.

doi:10.1371/journal.pone.0107000

Crystal Structure of the Mineralocorticoid Receptor DNA Binding Domain in Complex with DNA

Journal Article · Thu Sep 04 00:00:00 EDT 2014 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0107000· OSTI ID:1627730

Hudson, William H. ^[1]; Youn, Christine ^[2]; Ortlund, Eric A. ^[2]

Emory University, Atlanta, GA (United States); DOE/OSTI
Emory University, Atlanta, GA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: AHA; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357; W-31109-ENG-38

OSTI ID:: 1627730

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 9 Vol. 9; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Crystal Structure of the Mineralocorticoid Receptor DNA Binding Domain in Complex with DNA

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