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Human olfactory receptor OR51E2 bound to propionate in complex with miniGs399Human olfactory receptor OR51E2 bound to propionate in complex with miniGs399
Structural highlights
FunctionO51E2_HUMAN Olfactory receptor (PubMed:27226631, PubMed:29249973). Activated by the odorant, beta-ionone, a synthetic terpenoid (PubMed:19389702, PubMed:27226631, PubMed:29249973). The activity of this receptor is probably mediated by G-proteins leading to the elevation of intracellular Ca(2+), cAMP and activation of the protein kinases PKA and MAPK3/MAPK1 (PubMed:27226631, PubMed:29249973). Stimulation of OR51E2 by beta-ionone affects melanocyte proliferation, differentiation, and melanogenesis (PubMed:27226631). Activation of OR51E2 by beta-ionone increases proliferation and migration of primary retinal pigment epithelial (RPE) cells (PubMed:29249973). Activated also by the short-chain fatty acids (SCFA) acetate and propionate. In response to SCFA, may positively regulate renin secretion and increase blood pressure (PubMed:23401498). May also be activated by steroid hormones and regulate cell proliferation (PubMed:19389702). Activated by L-lactate in glomus cells (By similarity).[UniProtKB:Q8VBV9][1] [2] [3] [4] Publication Abstract from PubMedOur sense of smell enables us to navigate a vast space of chemically diverse odour molecules. This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome(1-3). How odorants are recognized by odorant receptors remains unclear. Here we provide mechanistic insight into how an odorant binds to a human odorant receptor. Using cryo-electron microscopy, we determined the structure of the active human odorant receptor OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant-binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an odorant receptor. Molecular dynamics simulations demonstrate that propionate-induced conformational changes in extracellular loop 3 activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate odorant receptor, providing insight into how this large family of G protein-coupled receptors enables our olfactory sense. Structural basis of odorant recognition by a human odorant receptor.,Billesbolle CB, de March CA, van der Velden WJC, Ma N, Tewari J, Del Torrent CL, Li L, Faust B, Vaidehi N, Matsunami H, Manglik A Nature. 2023 Mar;615(7953):742-749. doi: 10.1038/s41586-023-05798-y. Epub 2023 , Mar 15. PMID:36922591[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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