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Author Notes:

E-mail: eortlun@emory.edu

Conceived and designed the experiments: WHH EAO. Performed the experiments: WHH CY. Analyzed the data: WHH EAO. Contributed to the writing of the manuscript: WHH EAO.

X-ray data were collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at www.ser-cat.org/members.html.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38.

This work was supported by the AHA 13PRE16920012 and NIH 5T32GM008602-14. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • GLUCOCORTICOID-RECEPTOR
  • MOLECULAR-MECHANISMS
  • RESPONSE ELEMENTS
  • CARDIAC FIBROSIS
  • CANCER GENOMICS
  • MESSENGER-RNAS
  • HEART-FAILURE
  • CROSS-TALK
  • MUTATIONS
  • CELLS

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

Tools:

Journal Title:

PLoS ONE

Volume:

Volume 9, Number 9

Publisher:

, Pages e107000-e107000

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2014 Hudson et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits making multiple copies, distribution of derivative works, distribution, public display, and publicly performance, provided the original work is properly cited. This license requires credit be given to copyright holder and/or author, copyright and license notices be kept intact.

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