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- W4292056146 abstract "RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT2C isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT2C-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities." @default.
- W4292056146 created "2022-08-17" @default.
- W4292056146 creator A5007856961 @default.
- W4292056146 creator A5041661036 @default.
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- W4292056146 date "2022-08-01" @default.
- W4292056146 modified "2023-10-09" @default.
- W4292056146 title "Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors" @default.
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- W4292056146 doi "https://doi.org/10.1016/j.celrep.2022.111211" @default.
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