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NMR Spectroscopy for the Characterization of GPCR Energy Landscapes

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Structure and Function of GPCRs

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 30))

Abstract

G protein-coupled receptor (GPCR)-mediated signal transduction has a central role in human physiology and implication in many diseases. Despite the tremendous number of X-ray crystallography structures published in the past decade, the molecular mechanisms of ligand-dependent signaling remain to be completed. In particular, very little information is available concerning the implication of receptor dynamics and conformational changes on GPCR ligand efficiency and coupling. In this context, mapping the conformational landscape of GPCRs, and how it is modulated by the membrane environment and allosteric and signaling partners, is fundamental in order to gain a clear picture of how the signaling mechanism proceeds. Solution-state nuclear magnetic resonance (NMR) is a powerful technique to study GPCR energy landscapes, i.e., conformational ensembles along activation and inactivation pathway, and associated kinetic barriers.

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Abbreviations

β-DDM:

n-Dodecyl-beta-maltoside

BLT2:

Leukotriene B4 human receptor 2

DEER:

Double electron–electron resonance

GPCR:

G protein-coupled receptor

LMNG:

Lauryl maltose neopentyl glycol

MD:

Molecular dynamics

MNG-3:

Maltose neopentyl glycol-3

NB:

Nano-bodies

NMR:

Nuclear magnetic resonance

SDS:

Sodium dodecyl sulfate

TET:

Trifluoroethylthiol

TM:

Transmembrane

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Authors and Affiliations

  1. Laboratory of Physical and Chemical Biology of Membrane Proteins, Institut de Biologie Physico-Chimique (IBPC), UMR 7099 CNRS, Paris, France

    Marina Casiraghi & Laurent J. Catoire

  2. Paris Diderot University, Paris, France

    Marina Casiraghi & Laurent J. Catoire

  3. PSL Research University, Paris, France

    Marina Casiraghi & Laurent J. Catoire

  4. Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS – Université Montpellier – ENSCM, Montpellier, France

    Jean-Louis Banères

Authors
  1. Marina Casiraghi
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  2. Jean-Louis Banères
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  3. Laurent J. Catoire
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Correspondence to Laurent J. Catoire .

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  1. Institut de Génomique Fonctionnelle Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Montpellier, Montpellier, France

    Guillaume Lebon

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Casiraghi, M., Banères, JL., Catoire, L.J. (2017). NMR Spectroscopy for the Characterization of GPCR Energy Landscapes. In: Lebon, G. (eds) Structure and Function of GPCRs. Topics in Medicinal Chemistry, vol 30. Springer, Cham. https://doi.org/10.1007/7355_2017_31

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