Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor
UNC Libraries June 7, 2024 Kami Kim, T Che, Ouliana Panova et al.
Psychedelics such as LSD, psilocybin, and related compounds are used recreationally and are being investigated as treatments for depression, anxiety, and substance abuse. Their therapeutic and hallucinogenic effects depend on activating the 5-HT2A serotonin receptor, but the molecular details were unclear. Using cryo-electron microscopy and X-ray crystallography, researchers determined the structures of the 5-HT2A receptor bound to a hallucinogen, LSD, and an inverse agonist. These structures reveal how the receptor interacts with Gαq protein and changes shape when activated. The findings may guide development of more selective drugs for neuropsychiatric disorders.