Source:http://linkedlifedata.com/resource/pubmed/id/12456792
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| Predicate | Object |
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| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
2002-11-28
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| pubmed:abstractText |
Nuclear receptors form strong dimers that are essential for their function as transcription factors, and it is thought that ligand binding can affect dimer stability. In this report, we describe convenient fluorescence resonance energy transfer (FRET)-based methods for measuring the thermodynamic and kinetic stability of dimers of the estrogen receptor-alpha ligand-binding domain (ERalpha-LBD). We have developed receptors that are chemically labeled with a single fluorophore in a site-specific manner. These fluorophore-labeled ERs are functional and can be used to measure directly the affinity and stability of ERalpha-LBD dimers. Our results indicate that unliganded ERalpha-LBDs exist as very stable dimers and that the dissociation rate of these dimers is slow (t(1/2)=39 +/- 3 min at 28 C) and is further slowed (< or =7-fold) by the addition of various ligands. Estrogen antagonists provide greater kinetic stabilization of the ER dimers than agonists. In addition, coactivator peptides containing the LXXLL motif selectively stabilize agonist-bound ERalpha-LBD dimers. These fluorescence-based assays for measuring the kinetic and thermodynamic stability of ER dimers provide a functional in vitro method for assessing the agonist or antagonist character of novel ligands.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/NCOA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium
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| pubmed:status |
MEDLINE
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| pubmed:author | |
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2706-19
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| pubmed:dateRevised |
2009-11-19
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| pubmed:articleTitle |
Estrogen receptor dimerization: ligand binding regulates dimer affinity and dimer dissociation rate.
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| pubmed:affiliation |
Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA.
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