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- PDB-7srq: 5-HT2B receptor bound to LSD obtained by cryo-electron microscopy... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7srq | ||||||
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Title | 5-HT2B receptor bound to LSD obtained by cryo-electron microscopy (cryoEM) | ||||||
![]() | 5-hydroxytryptamine receptor 2B | ||||||
![]() | MEMBRANE PROTEIN / 5-HT2B receptor / serotonin receptor / GPCR / Lysergic acid diethylamide / LSD / cryoEM | ||||||
Function / homology | ![]() intestine smooth muscle contraction / Gq/11-coupled serotonin receptor activity / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / regulation of behavior / G protein-coupled serotonin receptor complex / Serotonin receptors / serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / G protein-coupled serotonin receptor activity ...intestine smooth muscle contraction / Gq/11-coupled serotonin receptor activity / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / regulation of behavior / G protein-coupled serotonin receptor complex / Serotonin receptors / serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / G protein-coupled serotonin receptor activity / serotonin receptor signaling pathway / embryonic morphogenesis / serotonin binding / vasoconstriction / cardiac muscle hypertrophy / neural crest cell migration / neural crest cell differentiation / cGMP-mediated signaling / neurotransmitter receptor activity / positive regulation of cell division / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / G-protein alpha-subunit binding / heart morphogenesis / release of sequestered calcium ion into cytosol / positive regulation of endothelial cell proliferation / ERK1 and ERK2 cascade / GTPase activator activity / positive regulation of cytokine production / calcium-mediated signaling / intracellular calcium ion homeostasis / chemical synaptic transmission / G alpha (q) signalling events / positive regulation of canonical NF-kappaB signal transduction / positive regulation of ERK1 and ERK2 cascade / G protein-coupled receptor signaling pathway / response to xenobiotic stimulus / positive regulation of cell population proliferation / dendrite / synapse / negative regulation of apoptotic process / nucleoplasm / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||
![]() | Barros-Alvarez, X. / Cao, C. / Panova, O. / Roth, B.L. / Skiniotis, G. | ||||||
Funding support | 1items
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![]() | ![]() Title: Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. 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 / ...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 / ![]() 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 75.2 KB | Display | ![]() |
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PDB format | ![]() | 49.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 724.7 KB | Display | ![]() |
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Full document | ![]() | 726.3 KB | Display | |
Data in XML | ![]() | 15.7 KB | Display | |
Data in CIF | ![]() | 21.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 25401MC ![]() 7srrC ![]() 7srsC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 35052.629 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Sugar | ChemComp-NAG / |
#3: Chemical | ChemComp-7LD / ( |
Has ligand of interest | Y |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: 5-HT2B receptor bound to LSD / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Conc.: 6.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 55000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 1.23 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 8491352 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 665475 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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