MT1 Melatonin Receptor Reconstitution in Nanodiscs

Methods Mol Biol. 2022:2550:171-178. doi: 10.1007/978-1-0716-2593-4_21.

Abstract

A way to study G protein-coupled receptors in a minimal system is to reconstruct artificial membrane mimics, made of detergent and/or of lipids in which the purified receptor is maintained. In particular, it is now possible to generate lipid nanoparticles, such as nanodiscs, in which a single receptor molecule is included. Such objects offer the invaluable potential of studying an isolated receptor stabilized in a finely controlled membrane-like environment to evaluate its pharmacology, its function, and its structure at the molecular level. In this chapter, we detail the different steps from the extraction and isolation of a recombinant MT1 melatonin receptor in detergent, down to its reconstitution into nanodiscs. A G protein activation test is further described in order to exemplify how the functionality of such particles may be investigated.

Keywords: Activation; Detergent; G protein; MT1 receptor; Nanodiscs; Reconstitution; Solubilization.

MeSH terms

  • Detergents / chemistry
  • GTP-Binding Proteins / metabolism
  • Lipids / chemistry
  • Liposomes
  • Melatonin*
  • Membranes, Artificial
  • Nanoparticles
  • Receptor, Melatonin, MT1* / genetics
  • Receptor, Melatonin, MT1* / metabolism

Substances

  • Detergents
  • Lipid Nanoparticles
  • Lipids
  • Liposomes
  • Membranes, Artificial
  • Receptor, Melatonin, MT1
  • GTP-Binding Proteins
  • Melatonin