FRET-based binding assay between a fluorescent cAMP analogue and a cyclic nucleotide-binding domain tagged with a CFP

FEBS Lett. 2017 Sep;591(18):2869-2878. doi: 10.1002/1873-3468.12760. Epub 2017 Aug 20.

Abstract

The cyclic nucleotide-binding domain (CNBD) functions as a regulatory domain of many proteins involved in cyclic nucleotide signalling. We developed a straightforward and reliable binding assay based on intermolecular fluorescence resonance energy transfer (FRET) between an adenosine-3', 5'-cyclic monophosphate analogue labelled with fluorescein and a recombinant CNBD of human EPAC1 tagged with a cyan fluorescence protein (CFP). The high FRET efficiency of this method (~ 80%) allowed us to perform several types of binding experiments with nanomolar range of sample using conventional equipment. In addition, the CFP tag on the CNBD enabled us to perform a specific binding experiment using an unpurified protein. Considering these advantages, this technique is useful to study poorly characterized CNBDs.

Keywords: EPAC; binding experiment; equilibrium binding; molecular interaction.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay / methods*
  • Cyclic AMP / chemistry
  • Fluorescence Resonance Energy Transfer / methods*
  • Green Fluorescent Proteins / chemistry*
  • Guanine Nucleotide Exchange Factors / chemistry
  • Humans
  • Kinetics
  • Spectrometry, Fluorescence

Substances

  • Cyan Fluorescent Protein
  • Guanine Nucleotide Exchange Factors
  • RAPGEF3 protein, human
  • Green Fluorescent Proteins
  • Cyclic AMP