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.

• Publication year

  1986

• Venue

  Journal of Biological Chemistry

• Publication date

  1986-10-25

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0021-9258(18)66970-4PMID 3771517
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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