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pubmed-article:7578026pubmed:abstractTextPreviously, we have shown that the retinoid X receptor (RXR) forms tetramers with a high affinity and that interactions of the receptor with its ligand, 9-cis retinoic acid (9cRA), result in dissociation of protein tetramers. Here it is shown by fluorescence anisotropy studies that ligand-induced tetramer dissociation displays a pronounced positive cooperativity. The binding affinity of RXR for 9cRA at low saturation levels of the receptor with ligand was found to be significantly weaker than the affinity observed at higher levels of saturation. In addition, the rate of dissociation of 9cRA from RXR was found to be faster at low vs. high saturation levels of the receptor. These data suggest that the observed positive cooperativity of the ligand-induced dissociation of RXR tetramers stems from positive cooperativity in binding of 9cRA by the receptor. Kinetic studies showed that dissociation of RXR tetramers upon ligand binding is a rapid reaction characterized by a t1/2 of 80 ms, which is about 5 orders of magnitude faster than the rate of dissociation in the absence of ligand. The data indicate that the oligomeric state of RXR is tightly regulated by the precise concentrations of 9cRA and that it rapidly responds to changes in the ligand's concentrations. These findings further substantiate the hypothesis that modulation of the oligomeric state of RXR by 9cRA is an important regulatory step in the pathway by which retinoids affect gene transcription.lld:pubmed
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pubmed-article:7578026pubmed:pagination14263-9lld:pubmed
pubmed-article:7578026pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:7578026pubmed:articleTitleOn the role of ligand in retinoid signaling: positive cooperativity in the interactions of 9-cis retinoic acid with tetramers of the retinoid X receptor.lld:pubmed
pubmed-article:7578026pubmed:affiliationCornell University, Division of Nutritional Sciences, Ithaca, New York 14853-6301, USA.lld:pubmed
pubmed-article:7578026pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:7578026pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:7578026pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
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