7SRS

5-HT2B receptor bound to LSD in complex with beta-arrestin1 obtained by cryo-electron microscopy (cryoEM)

Summary for 7SRS

• Entry DOI: 10.2210/pdb7srs/pdb
• EMDB information: 25403
• Descriptor: Anti-5HT2BR Fab light chain, Anti-5HT2BR Fab heavy chain, 5-hydroxytryptamine receptor 2B, ... (8 entities in total)
• Functional Keywords: 5-ht2b receptor, serotonin receptor, beta-arrestin1, arrestin, gpcr, lysergic acid diethylamide, lsd, cryoem, membrane protein
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 150383.41

Authors

Barros-Alvarez, X.,Cao, C.,Panova, O.,Roth, B.L.,Skiniotis, G. (deposition date: 2021-11-08, release date: 2022-09-21, Last modification date: 2024-10-16)

Primary citation

Cao, C.,Barros-Alvarez, X.,Zhang, S.,Kim, K.,Damgen, M.A.,Panova, O.,Suomivuori, C.M.,Fay, J.F.,Zhong, X.,Krumm, B.E.,Gumpper, R.H.,Seven, A.B.,Robertson, M.J.,Krogan, N.J.,Huttenhain, R.,Nichols, D.E.,Dror, R.O.,Skiniotis, G.,Roth, B.L.
Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD.
Neuron, 110:3154-, 2022

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 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.

PubMed: 36087581
DOI: 10.1016/j.neuron.2022.08.006

Experimental method

ELECTRON MICROSCOPY (3.3 Å)