G protein-coupled receptor 37, member of the class A family of seven-transmembrane G protein-coupled receptors
GPR37, also called parkin-associated endothelin-like receptor (Pael-R), was isolated from a set of human brain frontal lobe expressed sequence tags. It is highly expressed in the mammalian CNS. It is a substrate of parkin and is involved in the pathogenesis of Parkinson's disease. GPR37 has recently been shown to act as a receptor for the neuropeptide prosaptide, the active fragment of the secreted neuroprotective and glioprotective factor prosaposin (also called sulfated glycoprotein-1). Both prosaptide and prosaposin protect primary astrocytes against oxidative stress. GPR37 is part of the class A family of GPCRs that includes receptors for hormones, neurotransmitters, sensory stimuli, and a variety of other ligands. 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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