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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jan 15;88(2):390–394. doi: 10.1073/pnas.88.2.390

Structural differences between the hormone and antihormone estrogen receptor complexes bound to the hormone response element.

M Sabbah 1, F Gouilleux 1, B Sola 1, G Redeuilh 1, E E Baulieu 1
PMCID: PMC50816  PMID: 1988939

Abstract

To investigate the molecular mechanism(s) by which the estrogen receptor (ER) modulates transcription, we compared the structures of receptor complexes containing estradiol, the agonist diethylstilbestrol, and the antagonist ICI164,384. The binding of ICI164,384 to nontransformed 8-9S ER does not preclude the salt-induced dissociation of the 90-kDa heat shock protein and releases the transformed homodimeric 5S ER as classically observed in the presence of agonist. We report that calf ER binds to the estrogen response element of the Xenopus vitellogenin A2 gene in either the absence or presence of hormone, agonist, or antagonist. These binding interactions were highly sequence- and receptor-specific. These findings indicate that ligand binding in vitro is not absolutely required for dimerization or specific DNA binding of the ER. As demonstrated by gel retardation assays, the ICI164,384-ER complex bound to the response element displays a slower mobility than complexes formed in the presence of estradiol or agonist. This difference in electrophoretic mobility is suggestive of a conformational change in the complex induced by the ligand. An exchange experiment demonstrated that this alteration of the structure is reversible. We suggest that ICI164,384 induces conformational modifications within the ligand-binding domain of the receptor that do not prevent binding to the response element but could fail to promote subsequent events required for gene transcription.

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Selected References

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