Families Of Gpcrs

The overall amino acid sequence homology among GPCRs is rather low. Certain homologous regions arise from sequence alignment of the 7TMs within the GPCR families. The largest group of GPCRs is designated family A or class 1 and consists of light receptors (rhodopsin), adrenaline (adrenergic) receptors, and olfactory receptors. Every member shows a highly conserved arginine in the Asp-Arg-Tyr (DRY) motif6 located at the cytoplasmic side of the third transmembrane domain (TM3).

Approximately 25 peptide hormone and neuropeptide receptors belong to family B or class 2. They include secretin, glucagon and vasoactive intestinal peptides, calcitonin, and corticotrophin-releasing hormone. Family B GPCRs generally couple through the Gs G protein-activating adenylyl cyclase. The family C receptors consist of the metabotropic glutamate receptors (mGluRs), the g-amino butyric acid (GABA) receptors, the calcium-sensing receptor, and certain taste receptors. Their typical feature is an exceptionally large extracellular N-terminal region that plays a crucial role in ligand binding and receptor activation. Additionally, the yeast pheromone receptors and the cAMP receptors from Dictyostelium discoideum form three smaller families designated D, E, and F. The classification of GPCRs (including the novel GRAFS system) is described in more detail in Chapter 10.

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