[How do G-protein-coupled receptors work? The case of metabotropic glutamate and GABA receptors].
G-protein coupled receptors (GPCRs) represent the largest membrane proteins family in animal genomes. Being the receptors for most hormones and neurotransmitters, these proteins play a central role in intercellular communication. GPCRs can be classified into several groups based on the sequence similarity of their common structural feature: the heptahelical domain. The metabotropic receptors for the main neurotransmitters glutamate and gamma-aminobutyric acid (GABA) belong to the class III of GPCRs, together with others receptors for Ca2+, for sweet and amino acid taste compounds and for some pheromones, as well as for odorants in fish. Besides their transmembrane heptahelical domain responsible for G-protein activation, most of class III receptors possess a large extracellular domain responsible for ligand recognition. The recent resolution of the structure of this binding domain of one of these receptors, the mGlu1 receptor, together with the recent demonstration that these receptors are dimers, revealed an original mechanism of activation for these GPCRs. Such data open new possibilities to develop drugs aimed at modulating these receptors, and raised a number of interesting questions on the activation mechanism of other GPCRs.
Galvez
Thierry
T
Center for Clinical Sciences Research, Department of Molecular Pharmacology, Stanford University Medical Center, 269, Campus Drive, Room 3230, Stanford, CA 94305, USA. galvez@stanford.edu
Pin
Jean-Philippe
JP
D000818:Animals; D019281:Dimerization; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018079:Receptors, GABA / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018079:Receptors, GABA; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins