[English] 日本語
![](img/lk-miru.gif)
- PDB-6wha: HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 6wha | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein, beta/gamma subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) | |||||||||
![]() |
| |||||||||
![]() | MEMBRANE PROTEIN/IMMUNE SYSTEM / 5HT2A / G protein / 25-CN-NBOH / GPCR / cryo-EM / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() positive regulation of heat generation / protein localization to cytoskeleton / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / neurofilament / positive regulation of cytokine production involved in immune response ...positive regulation of heat generation / protein localization to cytoskeleton / 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding / Gq/11-coupled serotonin receptor activity / phospholipase C-activating serotonin receptor signaling pathway / positive regulation of phosphatidylinositol biosynthetic process / G protein-coupled serotonin receptor signaling pathway / G protein-coupled serotonin receptor complex / neurofilament / positive regulation of cytokine production involved in immune response / artery smooth muscle contraction / Serotonin receptors / cell body fiber / serotonin receptor signaling pathway / sensitization / urinary bladder smooth muscle contraction / protein tyrosine kinase activator activity / serotonin binding / negative regulation of synaptic transmission, glutamatergic / G protein-coupled serotonin receptor activity / positive regulation of platelet aggregation / : / neurotransmitter receptor activity / temperature homeostasis / positive regulation of DNA biosynthetic process / positive regulation of fat cell differentiation / regulation of dopamine secretion / positive regulation of execution phase of apoptosis / negative regulation of potassium ion transport / detection of temperature stimulus involved in sensory perception of pain / positive regulation of vasoconstriction / behavioral response to cocaine / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / detection of mechanical stimulus involved in sensory perception of pain / release of sequestered calcium ion into cytosol / presynaptic modulation of chemical synaptic transmission / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of glycolytic process / dendritic shaft / caveola / glycolytic process / electron transport chain / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / memory / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / G alpha (z) signalling events / positive regulation of inflammatory response / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / positive regulation of peptidyl-tyrosine phosphorylation / G-protein beta-subunit binding / positive regulation of neuron apoptotic process / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / virus receptor activity / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / cytoplasmic vesicle / G alpha (s) signalling events / Ras protein signal transduction / G alpha (q) signalling events / chemical synaptic transmission / postsynaptic membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.36 Å | |||||||||
![]() | Skiniotis, G. / Roth, B. / Kim, K. / Panova, O. | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Structure of a Hallucinogen-Activated Gq-Coupled 5-HT Serotonin Receptor. Authors: Kuglae Kim / Tao Che / Ouliana Panova / Jeffrey F DiBerto / Jiankun Lyu / Brian E Krumm / Daniel Wacker / Michael J Robertson / Alpay B Seven / David E Nichols / Brian K Shoichet / Georgios ...Authors: Kuglae Kim / Tao Che / Ouliana Panova / Jeffrey F DiBerto / Jiankun Lyu / Brian E Krumm / Daniel Wacker / Michael J Robertson / Alpay B Seven / David E Nichols / Brian K Shoichet / Georgios Skiniotis / Bryan L Roth / ![]() Abstract: Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many ...Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions-both therapeutic and hallucinogenic-are not understood, although activation of the 5-HT serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state structure of HTR2A bound to 25-CN-NBOH-a prototypical hallucinogen-in complex with an engineered Gαq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gαq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 197.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 152.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 21669MC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 56167.309 Da / Num. of mol.: 1 Fragment: cybC (UNP residues 23-127) + linker + HTR2A (UNP residues 66-404) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: cybC, HTR2A, HTR2 / Production host: ![]() ![]() |
---|---|
#2: Protein | Mass: 28084.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules CD
#3: Protein | Mass: 39418.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|---|
#4: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody / Non-polymers , 2 types, 2 molecules E![](data/chem/img/U0G.gif)
![](data/chem/img/U0G.gif)
#5: Antibody | Mass: 28668.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|---|
#6: Chemical | ChemComp-U0G / |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: HTR2A bound to 25-CN-NBOH in complex with a mini-Galpha-q protein, beta/gamma subunits and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM) Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) | Organism: ![]() | ||||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | ||||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||||||||||||||
Buffer component |
| ||||||||||||||||||||||||||||||||||||
Specimen | Conc.: 16.7 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK II / Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Calibrated magnification: 57050 X / Calibrated defocus min: 1000 nm / Calibrated defocus max: 2500 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 4 sec. / Electron dose: 80 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2368 |
-
Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2712613 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.36 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 166497 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 59.95 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|