Résumé
mGlu and GABA
B
receptors belong to the class C G protein‐coupled receptors, together with receptors for Ca
2+
ions, for pheromone and sweet and umami taste compounds. They form dimers, either homo‐ (mGlu) or heterodimers (GABA
B
). The mechanism of activation of these receptors has been extensively studied in recent years, leading to a better understanding of the roles of the different domains of both protomers in the dimers. Each protomer is constituted of an extracellular domain (ECD) and a transmembrane domain (7TM) formed by seven transmembrane helices. In the ECD, a so‐called Venus flytrap module (VFT) recognizes the ligand and undergoes a modification of conformation that traps the ligand like a clamshell, and might undergo a second modification of conformation that induces a rotation of both VFTs, leading to the activation of the 7TM of the receptors and then to the activation of the G proteins. Except in GABA
B
receptor, a cystein‐rich domain (CRD) links the VFT to the 7TM and is likely crucial for the transmission of the active conformation information from the VFT toward the 7TM. The activation of the 7TM involves modification of interactions between TM helices and some crucial residues. Allosteric interactions between the different domains make the functioning of the dimeric receptors quite complex. Last but not least, only one of the two 7TMs is active at a time and able to activate the G proteins, as for the GABA
B
heterodimer, in which only GABA
B2
activates the G proteins, as has also been demonstrated for the homomeric mGlu receptor. This last decade, the discovery of compounds regulating receptors by acting at sites different from the endogenous ligand‐binding site led to the identification of positive and negative allosteric modulators. The general mechanisms are likely similar in most of the class C receptors. Copyright © 2011 John Wiley & Sons, Ltd.