EMD-25403
5-HT2B receptor bound to LSD in complex with beta-arrestin1 obtained by cryo-electron microscopy (cryoEM)
EMD-25403
Single-particle3.3 Å
Deposition: 08/11/2021Map released: 21/09/2022
Last modified: 16/10/2024
Sample Organism:
Mus musculus,
Homo sapiens
Sample: 5-HT2B receptor bound to LSD in complex with beta-arrestin1
Fitted models: 7srs (Avg. Q-score: 0.523)
Raw data: EMPIAR-11493
Deposition Authors: Barros-Alvarez X, Cao C, Panova O, Roth BL, Skiniotis G
Sample: 5-HT2B receptor bound to LSD in complex with beta-arrestin1
Fitted models: 7srs (Avg. Q-score: 0.523)
Raw data: EMPIAR-11493
Deposition Authors: Barros-Alvarez X, Cao C, Panova O, Roth BL, Skiniotis G
Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD.
Cao C,
Barros-Alvarez X,
Zhang S ,
Kim K,
Damgen MA,
Panova O,
Suomivuori CM ,
Fay JF,
Zhong X,
Krumm BE,
Gumpper RH,
Seven AB,
Robertson MJ,
Krogan NJ,
Huttenhain R ,
Nichols DE,
Dror RO ,
Skiniotis G ,
Roth BL
(2022) Neuron , 110 , 3154
,
Kim K,
Damgen MA,
Panova O,
Suomivuori CM ,
Fay JF,
Zhong X,
Krumm BE,
Gumpper RH,
Seven AB,
Robertson MJ,
Krogan NJ,
Huttenhain R ,
Nichols DE,
Dror RO ,
Skiniotis G ,
Roth BL
(2022) Neuron , 110 , 3154
Abstract:
Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT2A serotonin receptor (HTR2A), the 5-HT2B serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to its high expression and similarity to HTR2A. In this study, we determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. These structures provide distinct signaling snapshots of LSD's action, ranging from the transducer-free, partially active state to the transducer-coupled, fully active states. Insights from this study will both provide comprehensive molecular insights into the signaling mechanisms of the prototypical psychedelic LSD and accelerate the discovery of novel psychedelic drugs.
Serotonin (5-hydroxytryptamine [5-HT]) 5-HT2-family receptors represent essential targets for lysergic acid diethylamide (LSD) and all other psychedelic drugs. Although the primary psychedelic drug effects are mediated by the 5-HT2A serotonin receptor (HTR2A), the 5-HT2B serotonin receptor (HTR2B) has been used as a model receptor to study the activation mechanisms of psychedelic drugs due to its high expression and similarity to HTR2A. In this study, we determined the cryo-EM structures of LSD-bound HTR2B in the transducer-free, Gq-protein-coupled, and β-arrestin-1-coupled states. These structures provide distinct signaling snapshots of LSD's action, ranging from the transducer-free, partially active state to the transducer-coupled, fully active states. Insights from this study will both provide comprehensive molecular insights into the signaling mechanisms of the prototypical psychedelic LSD and accelerate the discovery of novel psychedelic drugs.