Cell-free expression, purification, and ligand-binding analysis of Drosophila melanogaster olfactory receptors DmOR67a, DmOR85b and DmORCO

Sci Rep. 2015 Jan 19:5:7867. doi: 10.1038/srep07867.

Abstract

Insects transmit numerous devastating diseases, including malaria, dengue fever, and sleeping sickness. Olfactory cues guide insects to their hosts, and are thus responsible for disease transmission. Understanding the molecular basis of insect olfaction could facilitate the development of interventions. The first step is to heterologously overexpress and purify insect olfactory receptors (ORs). This is challenging, as ORs are membrane proteins. Here, we show that insect ORs and their co-receptor can be expressed in an E. coli cell-free system. After immunoaffinity chromatography, the ORs are ~95% pure, and up to 1 mg/10 ml reaction is obtained. Circular dichroism together with microscale thermophoresis indicate that each receptor is properly folded, and can bind its respective ligand. This is the first time insect ORs have been expressed in an E. coli system. The methods described here could facilitate future structure-function studies, which may aid in developments to alleviate the suffering of millions caused by insect-transmitted diseases.

Publication types

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

MeSH terms

  • Animals
  • Cell-Free System
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / isolation & purification*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology
  • Escherichia coli / genetics
  • Gene Expression / genetics
  • Ligands
  • Olfactory Receptor Neurons / metabolism*
  • Protein Binding
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / isolation & purification*
  • Receptors, Odorant / biosynthesis
  • Receptors, Odorant / genetics
  • Receptors, Odorant / isolation & purification*

Substances

  • Drosophila Proteins
  • Ligands
  • Or67d protein, Drosophila
  • Orco protein, Drosophila
  • Receptors, Cell Surface
  • Receptors, Odorant