Probing conformational changes in the estrogen receptor: Evidence for a partially unfolded intermediate facilitating ligand binding and release

A. C. Gee, J. A. Katzenellenbogen

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Because the ligand bound to the ligand-binding domain (LBD) of nuclear hormone receptors is completely enveloped by protein, it is thought that the process of ligand binding or unbinding must involve a significant conformational change of this domain. We have used the intrinsic tryptophan fluorescence of the estrogen receptor-α (ERα) or estrogen receptor-β (ERβ) LBD, as well as bis-anilinonaphthalenesulfonate (bis-ANS), a probe for accessible interior regions of protein, to follow the guanidine-hydrochloride (Gua-HCl)-induced unfolding of this domain. In both cases, we find that the ER-LBD unfolding follows a two-phase process. At low Gua-HCl, the ER-LBD undergoes partial unfolding, whereas at high Gua-HCl, this domain undergoes a global unfolding, with bis-ANS binding preferentially to the partially unfolded state. The partially unfolded state of the ERα-LBD induced by denaturant does not bind ligand stably, but it may resemble an intermediate that this domain accesses transiently under native conditions that allow ligands to enter or exit the ligand-binding pocket.

Original languageEnglish (US)
Pages (from-to)421-428
Number of pages8
JournalMolecular Endocrinology
Volume15
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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