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National Institute of Environmental Health Sciences

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Publication Detail

Title: Conformational dynamics of estrogen receptors alpha and beta as revealed by intrinsic tryptophan fluorescence and circular dichroism.

Authors: Nair, S K; Thomas, T J; Greenfield, N J; Chen, A; He, H; Thomas, T

Published In J Mol Endocrinol, (2005 Oct)

Abstract: Estrogen receptors (ER alpha and ER beta) are ligand-activated nuclear receptors that mediate the action of estrogens. These receptors activate transcription by similar mechanism(s), although the overall amino acid sequence identity is only 47%. In order to compare the structural and conformational features of ER alpha and ER beta, we monitored their intrinsic tryptophan fluorescence during thermal unfolding. The 50% unfolding temperatures (T(M)) of ER alpha and ER beta were 39+/-1 and 40+/-2 degrees C, respectively. Estradiol had no significant effect on the T(M) of ER alpha or ER beta. In contrast, binding of the estrogen-response element increased the T(M) of ER alpha and ER beta by 10 degrees C. Thermal unfolding of estradiol-bound ER alpha and ligand-free ER beta showed two-step transitions, with the formation of intermediates that were stable between 36-48 and 34-42 degrees C, respectively. We confirmed the presence of intermediate states during thermal unfolding by circular dichroism spectroscopy. Atomic force microscopy showed that the ER beta intermediate consisted of discrete globular particles, whereas the ER alpha intermediate showed a speckled appearance, with sparse well-defined particles. Fluorescence-quenching studies showed the presence of two classes of tryptophan in unliganded ER alpha and ER beta. Binding of estradiol to ER beta exposed its tryptophans, whereas estradiol reduced the accessibility of the tryptophans of ER alpha. Our results illustrate the differential effects of ligands on the unfolding of ER alpha and ER beta, and identify partially unfolded intermediates. Differences in the conformational flexibility and stability of ER alpha and ER beta may represent functional differences of ligand-bound ERs in recruiting coactivator proteins and initiating transcription.

PubMed ID: 16216903 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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