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Yorodumi- PDB-8k8j: Cannabinoid Receptor 1 bound to Fenofibrate coupling MiniGsq and ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8k8j | ||||||
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Title | Cannabinoid Receptor 1 bound to Fenofibrate coupling MiniGsq and Nb35 Complex | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / GPCR | ||||||
Function / homology | Function and homology information cannabinoid signaling pathway / regulation of penile erection / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / negative regulation of mast cell activation / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / negative regulation of fatty acid beta-oxidation / negative regulation of dopamine secretion / positive regulation of acute inflammatory response to antigenic stimulus / negative regulation of serotonin secretion ...cannabinoid signaling pathway / regulation of penile erection / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / negative regulation of mast cell activation / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / negative regulation of fatty acid beta-oxidation / negative regulation of dopamine secretion / positive regulation of acute inflammatory response to antigenic stimulus / negative regulation of serotonin secretion / regulation of feeding behavior / regulation of presynaptic cytosolic calcium ion concentration / negative regulation of action potential / Class A/1 (Rhodopsin-like receptors) / positive regulation of blood pressure / positive regulation of fever generation / regulation of metabolic process / axonal fasciculation / regulation of synaptic transmission, GABAergic / PKA activation in glucagon signalling / regulation of insulin secretion / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / GABA-ergic synapse / maternal process involved in female pregnancy / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to nutrient / regulation of synaptic transmission, glutamatergic / adenylate cyclase activator activity / negative regulation of blood pressure / trans-Golgi network membrane / response to cocaine / G protein-coupled receptor activity / electron transport chain / response to nicotine / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / cognition / platelet aggregation / 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 / positive regulation of neuron projection development / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / 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 / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / glucose homeostasis / sensory perception of smell / actin cytoskeleton / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / presynaptic membrane / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / growth cone / fibroblast proliferation / G alpha (s) signalling events / spermatogenesis Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Escherichia coli (E. coli) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.88 Å | ||||||
Authors | Tang, W.Q. / Wang, T.X. / Li, F.H. / Wang, J.Y. | ||||||
Funding support | China, 1items
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Citation | Journal: Adv Sci (Weinh) / Year: 2024 Title: Fenofibrate Recognition and G Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1. Authors: Tianxin Wang / Wenqin Tang / Ziyi Zhao / Ran Zhao / Zhenyu Lv / Xuzhen Guo / Quanchang Gu / Boxiang Liu / Haoyu Lv / Jiayan Chen / Kaiquan Zhang / Fahui Li / Jiangyun Wang / Abstract: The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-G complexes ...The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-G complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and G coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-G complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and G protein coupling by CB1 and will facilitate future drug discovery and design. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8k8j.cif.gz | 224.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8k8j.ent.gz | 170.8 KB | Display | PDB format |
PDBx/mmJSON format | 8k8j.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8k8j_validation.pdf.gz | 478.6 KB | Display | wwPDB validaton report |
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Full document | 8k8j_full_validation.pdf.gz | 490.4 KB | Display | |
Data in XML | 8k8j_validation.xml.gz | 21.5 KB | Display | |
Data in CIF | 8k8j_validation.cif.gz | 32.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k8/8k8j ftp://data.pdbj.org/pub/pdb/validation_reports/k8/8k8j | HTTPS FTP |
-Related structure data
Related structure data | 36951MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
Experimental dataset #1 | Data reference: 10.6019/EMPIAR-11642 / Data set type: EMPIAR |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 30652.561 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Escherichia coli (E. coli) / References: UniProt: P63092 |
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#2: Protein | Mass: 37416.930 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873 |
#3: Protein | Mass: 10497.960 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768 |
-Antibody / Protein / Non-polymers , 3 types, 3 molecules NR
#4: Antibody | Mass: 15271.938 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) |
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#5: Protein | Mass: 59685.355 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human) Gene: cybC, CNR1, CNR / Production host: Homo sapiens (human) / References: UniProt: P0ABE7, UniProt: P21554 |
#6: Chemical | ChemComp-J3O / Mass: 360.831 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H21ClO4 / Feature type: SUBJECT OF INVESTIGATION |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cannabinoid Receptor 1-G protein complex / Type: COMPLEX / Entity ID: #5, #1-#4 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.88 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 352452 / Symmetry type: POINT | ||||||||||||||||||||||||
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