orphan G protein-coupled receptors 153 and 162, member of the class A family of seven-transmembrane G protein-coupled receptors
This group contains the G-protein coupled receptor 153 (GPR153), GPR162, and similar proteins. These are orphan GCPRs with unknown endogenous ligand and function. GPR153 and GPR163 are widely expressed in the central nervous system (CNS) and share a common evolutionary ancestor due to a gene duplication event. Although categorized as members of the rhodopsin-like class A GPCRs, both GPR162 and GPR153 contain an HRM-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors which is important for efficient G protein-coupled signal transduction. Moreover, the LPxF motif, a variant of NPxxY motif that plays a crucial role during receptor activation, is found at the end of TM7 in both GPR162 and GPR153. 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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