G protein-coupled estrogen receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors
G-protein coupled estrogen receptor 1 (GPER1), also known as the G-protein coupled receptor 30 (GPR30), is a high affinity receptor for estrogen. This receptor is a member of the class A of seven-transmembrane GPCRs. Estrogen binding results in intracellular calcium mobilization and synthesis of phosphatidylinositol (3,4,5)-trisphosphate in the nucleus. GPR30 plays an important role in development of tamoxifen resistance in breast cancer cells. The distribution of GPR30 is well established in the rodent, with high expression observed in the hypothalamus, pituitary gland, adrenal medulla, kidney medulla and developing follicles of the ovary. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.
Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
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