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Mol Cell Endocrinol. 2019 Mar 15;484:69-77. doi: 10.1016/j.mce.2018.12.019. Epub 2019 Jan 25.

NMR analysis of GPCR conformational landscapes and dynamics.

Author information

1
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR7099, CNRS/Université; Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550), 13 rue Pierre et Marie Curie, 75005, Paris, France.
2
Institut des Biomoléćules Max Mousseron (IBMM), UMR 5247 CNRS, Université; Montpellier, ENSCM, 15 av. Charles Flahault, 34093, Montpellier, France.
3
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR7099, CNRS/Université; Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique (FRC 550), 13 rue Pierre et Marie Curie, 75005, Paris, France. Electronic address: laurent.catoire@ibpc.fr.

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.

KEYWORDS:

Energy landscape; GPCR; NMR

PMID:
30690069
DOI:
10.1016/j.mce.2018.12.019

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