The activation mechanism of class-C G-protein coupled receptors.
Class-C G-protein coupled receptors (GPCRs) represent a distant group among the large family of GPCRs. This class includes the receptors for the main neurotransmitters, glutamate and gamma-aminobutyric acid (GABA), and the receptors for Ca(2+), some taste and pheromone molecules, as well as some orphan receptors. Like any other GPCRs, class-C receptors possess a heptahelical domain (HD) involved in heterotrimeric G-protein activation, but most of them also have a large extracellular domain (ECD) responsible for agonist recognition and binding. In addition, it is now well accepted that these receptors are dimers, either homo or heterodimers. This complex architecture raises a number of important questions. Here we will discuss our view of how agonist binding within the large ECD triggers the necessary change of conformation, or stabilize a specific conformation, of the heptahelical domain leading to G-protein activation. How ligands acting within the heptahelical domain can change the properties of these complex macromolecules.
Pin
J-P
JP
Lab. of Functional Genomic, Dept. of Molecular Pharmacology, CNRS UPR-2580, 141 rue de la Cardonille, 34094 Montpellier Cedex 5, France. jppin@ccipe.cnrs.fr
Kniazeff
J
J
Goudet
C
C
Bessis
A-S
AS
Liu
J
J
Galvez
T
T
Acher
F
F
Rondard
P
P
Prézeau
L
L
D000495:Allosteric Site; D000818:Animals; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000737:chemistry
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid