Dimers and beyond: The functional puzzles of class C GPCRs.
Our understanding of G protein-coupled receptor (GPCR) activation has evolved during the last ten years, both at a molecular level thanks to the resolution of several crystal structures, and at a cellular level with the characterization of complexes surrounding the receptor. Class C GPCRs, including receptors for glutamate, γ-aminobutyric acid (GABA), taste compounds, amino acids and Ca(2+), have several structural features that make them unique in the GPCR family. First, they possess a large and structurally-defined extracellular domain, which is distal from the transmembrane core and bears the agonist binding site. Second, they form obligatory dimers providing a unique mode of activation compared to GPCRs of other classes. In this article, we aim to provide an overview of the molecular mechanisms of class C GPCR activation as dimeric entities. Furthermore, we discuss the possibility of modulating receptor function through the use of ligands or by association, direct or indirect, with other receptors (GPCRs or not) with the aim to better understand receptor function. Finally, we present the therapeutic scope for the class C GPCRs that highlights the need to fully characterize the functioning of these receptors in their native environment to develop better therapeutic molecules.
CNRS UMR 5203, INSERM U661 and Université Montpellier 1, 2, Institut de Génomique Fonctionnelle, 141 rue de la Cardonille, F-34094 Montpellier Cedex 05, France. julie.kniazeff@igf.cnrs.fr
Julie
J
Kniazeff
Laurent
L
Prézeau
Philippe
P
Rondard
Jean-Philippe
JP
Pin
Cyril
C
Goudet
D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000145:classification / Q000502:physiology*; D013237:Stereoisomerism
D008024:Ligands; D043562:Receptors, G-Protein-Coupled