Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors
Ryan H. Gumpper, Jonathan F. Fay, Bryan L. Roth
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.
Topics & Concepts
RNA editingAgonistGene isoformRNAG protein-coupled receptorBiologyInverse agonistReceptorCell biologyComputational biologyBiochemistryGeneRNA regulation and diseaseRNA and protein synthesis mechanismsProtein Structure and Dynamics