DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex

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dc.contributor.authorZhang, J.
dc.contributor.authorChalmers, M.
dc.contributor.authorStayrook, K.
dc.contributor.authorBurris, L.
dc.contributor.authorWang, Y.
dc.contributor.authorBusby, S.
dc.contributor.authorPascal, B.
dc.contributor.authorGarcia-Ordonez, R.
dc.contributor.authorBruning, J.
dc.contributor.authorIstrate, M.
dc.contributor.authorKojetin, D.
dc.contributor.authorDodge, J.
dc.contributor.authorBurris, T.
dc.contributor.authorGriffin, P.
dc.date.issued2011
dc.description.abstractThe 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.
dc.description.statementofresponsibilityJun 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
dc.identifier.citationNature Structural and Molecular Biology, 2011; 18(5):556-563
dc.identifier.doi10.1038/nsmb.2046
dc.identifier.issn1545-9985
dc.identifier.issn1545-9985
dc.identifier.orcidBruning, J. [0000-0002-6919-1824]
dc.identifier.urihttp://hdl.handle.net/2440/75446
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2011 Nature America, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1038/nsmb.2046
dc.subjectHumans
dc.subjectTretinoin
dc.subjectDihydroxycholecalciferols
dc.subjectRetinoid X Receptors
dc.subjectReceptors, Calcitriol
dc.subjectLigands
dc.subjectProtein Interaction Mapping
dc.subjectBinding Sites
dc.subjectProtein Structure, Tertiary
dc.subjectModels, Molecular
dc.subjectProtein Interaction Domains and Motifs
dc.subjectPromoter Regions, Genetic
dc.subjectProtein Stability
dc.subjectNuclear Receptor Coactivator 1
dc.subjectAlitretinoin
dc.titleDNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex
dc.typeJournal article
pubs.publication-statusPublished

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