Abstract

Among membrane-bound receptors, the G protein-coupled receptors (GPCRs) are certainly the most diverse. They have been very successful during evolution, being capable of transducing messages as different as photons, organic odorants, nucleotides, nucleosides, peptides, lipids and proteins. Indirect studies, as well as two-dimensional crystallization of rhodopsin, have led to a useful model of a common 'central core', composed of seven transmembrane helical domains, and its structural modifications during activation. There are at least six families of GPCRs showing no sequence similarity. They use an amazing number of different domains both to bind their ligands and to activate G proteins. The fine-tuning of their coupling to G proteins is regulated by splicing, RNA editing and phosphorylation. Some GPCRs have been found to form either homo- or heterodimers with a structurally different GPCR, but also with membrane-bound proteins having one transmembrane domain such as nina-A, odr-4 or RAMP, the latter being involved in their targeting, function and pharmacology. Finally, some GPCRs are unfaithful to G proteins and interact directly, via their C-terminal domain, with proteins containing PDZ and Enabled/VASP homology (EVH)-like domains.