Structural insights into constitutive activity of 5-HT₆ receptor.

ABSTRACT: While most therapeutic research on G-protein-coupled receptors (GPCRs) focuses on receptor activation by (endogenous) agonists, significant therapeutic potential exists through agonist-independent intrinsic constitutive activity that can occur in various physiological and pathophysiological settings. For example, inhibiting the constitutive activity of 5-HT₆R-a receptor that is found almost exclusively in the brain and mediates excitatory neurotransmission-has demonstrated a therapeutic effect on cognitive/memory impairment associated with several neuropsychiatric disorders. However, the structural basis of such constitutive activity remains unclear. Here, we present a cryo-EM structure of serotonin-bound human 5-HT₆R-Gs heterotrimer at 3.0-Å resolution. Detailed anal

SUBMITTER: He L 

PROVIDER: S-EPMC10083584 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature