Research on the structure, regulation and signalling properties of the family of seven-transmembrane-helix, heterotrimeric guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs) continues at a frantic pace. This reflects their central role in transmission of hormone- and neurotransmitter-encoded information across the plasma membrane of cells. The location of the ligand-binding sites on the extracellular face of the membrane has made them obvious targets for therapeutic intervention in a wide range of conditions resulting from endocrine imbalance. Furthermore, based on the identification of many novel GPCR sequences emerging from expressed sequence tags (ESTs) and other DNA sequencing programmes, it has become clear that the GPCR family is likely to be considerably larger than appreciated in even the recent past. Although neither the natural ligands nor synthetic pharmaceuticals have yet been identified for these so-called ;orphan' GPCRs, they offer the potential for a plethora of new therapeutic targets. Within a short review, it is impossible to cover all the current developments in this field and the topics selected represent a personal view of recent highlights of areas that provide both novel and general insights into the function and regulation of GPCRs.
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