Conformational transitions of the estrogen receptor monomer. Effects of estrogens, antiestrogen, and temperature.
The technique of aqueous two-phase partitioning has been used to study changes in estrogen receptor (ER) structure that occur upon ligand binding and/or heating in vitro. Studies with steroidal and nonsteroidal ligands indicate that the difference in partitioning properties between unoccupied and nontransformed ER is due to a ligand-induced change in this conformation of the protein. Furthermore, this conformational change is only partially induced by binding of 4-OH-tamoxifen. Although nontransformed 4-OH-tamoxifen complexes can be transformed by heat, there are significant differences in the transformation process for receptors bound to 4-OH-tamoxifen versus estrogenic ligands. A kinetic analysis of estrogen receptor transformation indicates that the process follows apparent first order kinetics, but is 2.5-fold slower for the 4-OH-tamoxifen-receptor complex. Direct heating of the unoccupied ER causes a significant change in receptor structure. Ligand binding to the heat-altered unoccupied receptor results in a further alteration of receptor structure. Experiments using polyethylene glycol palmitate indicate that the ligand-binding transition is associated with a reduction of the hydrophobic characteristics of the receptor. These results demonstrate that there are a number of independent conformational changes that occur within the monomeric ER steroid-binding subunit upon ligand binding and exposure to elevated temperature in vitro.
D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008433:Mathematics; D011487:Protein Conformation; D051381:Rats; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D013696:Temperature
D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D004970:Estrone; D004958:Estradiol; D004054:Diethylstilbestrol