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- EMDB-36951: Cannabinoid Receptor 1 bound to Fenofibrate coupling MiniGsq and ... -
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Open data
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Basic information
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Title | Cannabinoid Receptor 1 bound to Fenofibrate coupling MiniGsq and Nb35 Complex | |||||||||
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![]() | GPCR / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() 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 / regulation of feeding behavior ...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 / regulation of feeding behavior / negative regulation of serotonin secretion / 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 / regulation of insulin secretion / PKA activation in glucagon signalling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / GABA-ergic synapse / D1 dopamine receptor binding / maternal process involved in female pregnancy / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of synaptic transmission, glutamatergic / activation of adenylate cyclase activity / adenylate cyclase activator activity / negative regulation of blood pressure / response to nutrient / trans-Golgi network membrane / response to cocaine / G protein-coupled receptor activity / electron transport chain / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / response to nicotine / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / 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 / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / 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 / 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 / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / positive regulation of neuron projection development / 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 / sensory perception of smell / signaling receptor complex adaptor activity / actin cytoskeleton / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / glucose homeostasis / retina development in camera-type eye / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.88 Å | |||||||||
![]() | Tang WQ / Wang TX / Li FH / Wang JY | |||||||||
Funding support | ![]()
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 114.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16 KB 16 KB | Display Display | ![]() |
Images | ![]() | 64.3 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 487.4 KB | Display | ![]() |
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Full document | ![]() | 487 KB | Display | |
Data in XML | ![]() | 7 KB | Display | |
Data in CIF | ![]() | 8.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8k8jMC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Cannabinoid Receptor 1-G protein complex
Entire | Name: Cannabinoid Receptor 1-G protein complex |
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Components |
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-Supramolecule #1: Cannabinoid Receptor 1-G protein complex
Supramolecule | Name: Cannabinoid Receptor 1-G protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #5, #1-#4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 30.652561 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGHHHHHHEN LYFQGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RILHGGSGGS GGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF L NKQDLLAE ...String: MGHHHHHHEN LYFQGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RILHGGSGGS GGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF L NKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIRDEFLRIS TASGDGRHYC YPHFTCAVDT EN ARRIFND CKDIILQMNL REYNLV UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 10.49796 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHGGG SDSLEFIASK LAGGGSMASN NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFRE KKFFSAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Nanobody 35
Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.271938 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHHEPEA |
-Macromolecule #5: Soluble cytochrome b562,Cannabinoid receptor 1
Macromolecule | Name: Soluble cytochrome b562,Cannabinoid receptor 1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 59.685355 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHE NLYFQGGGRA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDA QKATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLLEVL F QGPVPADQ ...String: MKTIIALSYI FCLVFADYKD DDDAKLQTMH HHHHHHHHHE NLYFQGGGRA DLEDNWETLN DNLKVIEKAD NAAQVKDALT KMRAAALDA QKATPPKLED KSPDSPEMKD FRHGFDILVG QIDDALKLAN EGKVKEAQAA AEQLKTTRNA YIQKYLLEVL F QGPVPADQ VNITEFYNKS LSSFKENEEN IQCGENFMDI ECFMVLNPSQ QLAIAVLSLT LGTFTVLENL LVLCVILHSR SL RCRPSYH FIGSLAVADL LGSVIFVYSF IDFHVFHRKD SRNVFLFKLG GVTASFTASV GSLFLIAIDR YISIHRPLAY KRI VTRPKA VVAFCLMWTI AIVIAVLPLL GWNCEKLQSV CSDIFPHIDK TYLMFWIGVV SVLLLFIVYA YMYILWKAHS HAVR MIQRG TQKSIIIHTS EDGKVQVTRP DQARMDIELA KTLVLILVVL IICWGPLLAI MVYDVFGKMN KLIKTVFAFC SMLCL LNST VNPIIYALRS KDLRHAFRSM FPSCEGTAQP LDNSHHHHHH H UniProtKB: Soluble cytochrome b562, Cannabinoid receptor 1 |
-Macromolecule #6: propan-2-yl 2-[4-(4-chlorophenyl)carbonylphenoxy]-2-methyl-propanoate
Macromolecule | Name: propan-2-yl 2-[4-(4-chlorophenyl)carbonylphenoxy]-2-methyl-propanoate type: ligand / ID: 6 / Number of copies: 1 / Formula: J3O |
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Molecular weight | Theoretical: 360.831 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.88 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 352452 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |