G Protein-coupled Receptor (GPCR) Reconstitution and Labeling for Solution Nuclear Magnetic Resonance (NMR) Studies of the Structural Basis of Transmembrane Signaling

Molecules. 2022 Apr 20;27(9):2658. doi: 10.3390/molecules27092658.

Abstract

G protein-coupled receptors (GPCRs) are a large membrane protein family found in higher organisms, including the human body. GPCRs mediate cellular responses to diverse extracellular stimuli and thus control key physiological functions, which makes them important targets for drug design. Signaling by GPCRs is related to the structure and dynamics of these proteins, which are modulated by extrinsic ligands as well as by intracellular binding partners such as G proteins and arrestins. Here, we review some basics of using nuclear magnetic resonance (NMR) spectroscopy in solution for the characterization of GPCR conformations and intermolecular interactions that relate to transmembrane signaling.

Keywords: 19F-NMR; G protein-coupled receptors; amino-acid-specific NMR labeling; in-membrane chemical modification; membrane mimetics; sequence-specific NMR labeling; stable-isotope labeling.

Publication types

  • Review

MeSH terms

  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy / methods
  • Molecular Conformation
  • Receptors, G-Protein-Coupled* / metabolism
  • Signal Transduction*

Substances

  • Ligands
  • Receptors, G-Protein-Coupled