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NMR analysis of GPCR conformational landscapes and dynamics

Author:
Casiraghi, Marina, Point, Elodie, Pozza, Alexandre, Moncoq, Karine, Banères, Jean-Louis, Catoire, Laurent J.
Source:
Molecular and cellular endocrinology 2019 v.484 pp. 69-77
ISSN:
0303-7207
Subject:
G-protein coupled receptors, crystal structure, crystals, eukaryotic cells, microscopy, nuclear magnetic resonance spectroscopy, probability, signal transduction, structural biology
Abstract:
Understanding the signal transduction mechanism mediated by the G Protein-Coupled Receptors (GPCRs) in eukaryote cells represents one of the main issues in modern biology. At the molecular level, various biophysical approaches have provided important insights on the functional plasticity of these complex allosteric machines. In this context, X-ray crystal structures published during the last decade represent a major breakthrough in GPCR structural biology, delivering important information on the activation process of these receptors through the description of the three-dimensional organization of their active and inactive states. In complement to crystals and cryo-electronic microscopy structures, information on the probability of existence of different GPCR conformations and the dynamic barriers separating those structural sub-states is required to better understand GPCR function. Among the panel of techniques available, nuclear magnetic resonance (NMR) spectroscopy represents a powerful tool to characterize both conformational landscapes and dynamics. Here, we will outline the potential of NMR to address such biological questions, and we will illustrate the functional insights that NMR has brought in the field of GPCRs in the recent years.
Agid:
6284265