Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors
Ryan H. Gumpper, Jonathan F. Fay, Bryan L. Roth
Cell Reports August 1, 2022 DOI: 10.1016/j.celrep.2022.111211 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Structural biology and biochemical analysis Peer reviewed |
|---|---|
| Interventions | lorcaserin psilocin |
| Topics | Serotonin |
| Keywords | Rna editing Gene isoform G protein-coupled receptor Inverse agonist Cell biology Computational biology Biochemistry |
| Citations | 49 |
| Key points | RNA editing of intracellular loop 2 creates a hydrogen-bonding network that differentially modulates GPCR constitutive and agonist signaling activities across all 24 isoforms of the serotonin 2C receptor. |
Abstract
-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.