DNA binding alters coactivator interaction surfaces of the intact VDR–RXR complex
| Autor: | Thomas P. Burris, Bruce D. Pascal, Ruben D. Garcia-Ordonez, Jeffrey Alan Dodge, Monica A. Istrate, Michael J. Chalmers, Scott A. Busby, Yongjun Wang, Keith R. Stayrook, Patrick R. Griffin, Jun Zhang, Lorri L Burris, John B. Bruning, Douglas J. Kojetin |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular allosteric communication Response element Tretinoin Biology Retinoid X receptor Ligands Calcitriol receptor Article 03 medical and health sciences 0302 clinical medicine Nuclear Receptor Coactivator 1 Structural Biology Coactivator Protein Interaction Mapping Humans Protein Interaction Domains and Motifs Binding site co-activator binding surfaces Promoter Regions Genetic Molecular Biology Alitretinoin 030304 developmental biology 0303 health sciences Binding Sites Protein Stability DNA Cell biology Protein Structure Tertiary Nuclear receptor coactivator 1 Retinoid X Receptors Nuclear receptor Biochemistry 030220 oncology & carcinogenesis Small heterodimer partner Dihydroxycholecalciferols Receptors Calcitriol |
| Zdroj: | Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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