ABSTRACT
Acknowledgments ............................................................................................ 255
References ........................................................................................................ 255
Although remarkably diverse in sequence and function, all G protein-coupled
receptors (GPCRs) share a highly conserved topological arrangement of a seven-
transmembrane helical core domain joined by three intracellular loops, three extra-
cellular loops, and amino-and carboxyl-terminal domains.1 Overwhelming evidence
suggests that most, if not all, GPCRs have a strong propensity to dimerize and/or form
large oligomeric structures2 that can lead to cooperative binding of ligands to the
dimeric unit. A key event for the switch from inactive to active receptor is ligand-
induced conformational changes of transmembrane helices 6 (TM6), TM2, and
TM7.3 In turn, these helical movements alter the conformation of the intracellular
loops of the receptor to promote activation of associated heterotrimeric G proteins.