GPCR structural characterization by NMR spectroscopy in solution.

In the human proteome, 826 G-protein-coupled receptors (GPCRs) interact with extracellular stimuli to initiate cascades of intracellular signaling. Determining conformational dynamics and intermolecular interactions are key to understand GPCR function as a basis for drug design. X-ray crystallography and cryo-electron microscopy (cryo-EM) contribute molecular architectures of GPCRs and GPCR-signaling complexes. NMR spectroscopy is complementary by providing information on the dynamics of GPCR structures at physiological temperature. In this review, several NMR approaches in use to probe GPCR dynamics and intermolecular interactions are discussed. The topics include uniform stable-isotope labeling, amino acid residue-selective stable-isotope labeling, site-specific labeling by genetic engineering, the introduction of F-NMR probes, and the use of paramagnetic nitroxide spin labels. The unique information provided by NMR spectroscopy contributes to our understanding of GPCR biology and thus adds to the foundations for rational drug design.