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https://hdl.handle.net/2440/75446
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Type: | Journal article |
Title: | DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex |
Author: | Zhang, J. Chalmers, M. Stayrook, K. Burris, L. Wang, Y. Busby, S. Pascal, B. Garcia-Ordonez, R. Bruning, J. Istrate, M. Kojetin, D. Dodge, J. Burris, T. Griffin, P. |
Citation: | Nature Structural and Molecular Biology, 2011; 18(5):556-563 |
Publisher: | Nature Publishing Group |
Issue Date: | 2011 |
ISSN: | 1545-9985 1545-9985 |
Statement of Responsibility: | Jun Zhang, Michael J Chalmers, Keith R Stayrook, Lorri L Burris, Yongjun Wang, Scott A Busby, Bruce D Pascal, Ruben D Garcia-Ordonez, John B Bruning, Monica A Istrate, Douglas J Kojetin, Jeffrey A Dodge, Thomas P Burris & Patrick R Griffin |
Abstract: | The vitamin D receptor (VDR) functions as an obligate heterodimer in complex with the retinoid X receptor (RXR). These nuclear receptors are multidomain proteins, and it is unclear how various domains interact with one another within the nuclear receptor heterodimer. Here, we show that binding of intact heterodimer to DNA alters the receptor dynamics in regions remote from the DNA-binding domains (DBDs), including the coactivator binding surfaces of both co-receptors, and that the sequence of the DNA response element can determine these dynamics. Furthermore, agonist binding to the heterodimer results in changes in the stability of the VDR DBD, indicating that the ligand itself may play a role in DNA recognition. These data suggest a mechanism by which nuclear receptors show promoter specificity and have differential effects on various target genes, providing insight into the function of selective nuclear receptor modulators. |
Keywords: | Humans Tretinoin Dihydroxycholecalciferols Retinoid X Receptors Receptors, Calcitriol Ligands Protein Interaction Mapping Binding Sites Protein Structure, Tertiary Models, Molecular Protein Interaction Domains and Motifs Promoter Regions, Genetic Protein Stability Nuclear Receptor Coactivator 1 Alitretinoin |
Rights: | © 2011 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/nsmb.2046 |
Published version: | http://dx.doi.org/10.1038/nsmb.2046 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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