Application of Circular Dichroism Spectroscopy to the Analysis of the Interaction Between the Estrogen Receptor Alpha and Coactivators: The Case of Calmodulin

Methods Mol Biol. 2016:1366:241-259. doi: 10.1007/978-1-4939-3127-9_19.

Abstract

The estrogen receptor α ligand-binding domain (ERα-LBD) binds the natural hormone 17β-estradiol (E2) to induce transcription and cell proliferation. This process occurs with the contribution of protein and peptide partners (also called coactivators) that can modulate the structure of ERα, and therefore its specificity of action. As with most transcription factors, ERα exhibits a high content of α helix, making it difficult to routinely run spectroscopic studies capable of deciphering the secondary structure of the different partners under binding conditions. Ca(2+)-calmodulin, a protein also highly structured in α-helix, is a key coactivator for ERα activity. Here, we show how circular dichroism can be used to study the interaction of ERα with Ca(2+)-calmodulin. Our approach allows the determination not only of the conformational changes induced upon complex formation but also the dissociation constant (K d) of this interaction.

Keywords: Calmodulin; Circular dichroism; Estrogen receptor; Helix content; K d; Peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin / chemistry
  • Calmodulin / metabolism*
  • Circular Dichroism*
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / metabolism*
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Spectrometry, Mass, Electrospray Ionization
  • Structure-Activity Relationship
  • Workflow

Substances

  • Calmodulin
  • ESR1 protein, human
  • Estrogen Receptor alpha