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-Structure paper
Title | Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. |
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Journal, issue, pages | Neuron, Vol. 110, Issue 19, Page 3154-33167.e7, Year 2022 |
Publish date | Oct 5, 2022 |
Authors | Can Cao / Ximena Barros-Álvarez / Shicheng Zhang / Kuglae Kim / Marc A Dämgen / Ouliana Panova / Carl-Mikael Suomivuori / Jonathan F Fay / Xiaofang Zhong / Brian E Krumm / Ryan H Gumpper / Alpay B Seven / Michael J Robertson / Nevan J Krogan / Ruth Hüttenhain / David E Nichols / Ron O Dror / Georgios Skiniotis / Bryan L Roth / |
PubMed 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 ...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-HT serotonin receptor (HTR2A), the 5-HT 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. |
External links | Neuron / PubMed:36087581 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.7 - 3.3 Å |
Structure data | EMDB-25401, PDB-7srq: EMDB-25402, PDB-7srr: EMDB-25403, PDB-7srs: |
Chemicals | ChemComp-NAG: ChemComp-7LD: |
Source |
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Keywords | MEMBRANE PROTEIN / 5-HT2B receptor / serotonin receptor / GPCR / Lysergic acid diethylamide / LSD / cryoEM / G protein / beta-arrestin1 / arrestin |