[English] 日本語
Yorodumi
- PDB-23iw: Cannabinoid Receptor 1-Gi Complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 23iw
TitleCannabinoid Receptor 1-Gi Complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Cannabinoid receptor 1
  • Scfv16
KeywordsMEMBRANE PROTEIN/IMMUNE SYSTEM / Cannabinoid Receptor 1 / GPCR / membrane protein / active / MEMBRANE PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


cannabinoid signaling pathway / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / regulation of presynaptic cytosolic calcium ion concentration / axonal fasciculation / Class A/1 (Rhodopsin-like receptors) / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration ...cannabinoid signaling pathway / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / regulation of presynaptic cytosolic calcium ion concentration / axonal fasciculation / Class A/1 (Rhodopsin-like receptors) / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / mast cell degranulation / chemokine-mediated signaling pathway / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / response to peptide hormone / GABA-ergic synapse / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / glucose homeostasis / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / actin cytoskeleton / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / GDP binding / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / G-protein beta-subunit binding / extracellular vesicle / growth cone / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / GTPase binding / presynaptic membrane / G protein activity / midbody / Ca2+ pathway / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / ciliary basal body / mitochondrial outer membrane / Extra-nuclear estrogen signaling / membrane raft / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / centrosome / GTPase activity / synapse / GTP binding / protein-containing complex binding / glutamatergic synapse / magnesium ion binding / signal transduction
Similarity search - Function
Cannabinoid receptor type 1 / Cannabinoid receptor family / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit ...Cannabinoid receptor type 1 / Cannabinoid receptor family / G-protein alpha subunit, group I / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
: / Cannabinoid receptor 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.42 Å
AuthorsLiao, Y. / Zhang, Y.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell / Year: 2026
Title: Rational design of G-biased CB1 agonist with reduced side effects.
Authors: Yu-Ying Liao / Jinxin Che / Yun-Tao Gao / Jianheng Xue / Linjie Li / Lin-Lin Wu / Jia-Xue Hu / Meng-Ting Hu / Linghua Xie / Huibing Zhang / Dan-Dan Shen / Yingjun Dong / Shaokun Zang / Na ...Authors: Yu-Ying Liao / Jinxin Che / Yun-Tao Gao / Jianheng Xue / Linjie Li / Lin-Lin Wu / Jia-Xue Hu / Meng-Ting Hu / Linghua Xie / Huibing Zhang / Dan-Dan Shen / Yingjun Dong / Shaokun Zang / Na Zhang / Hao Wang / Yan Zhang / Xiaowu Dong / Xiao-Ming Li /
Abstract: The cannabinoid receptor 1 (CB1) has emerged as a promising candidate for next-generation non-opioid therapies. However, the development of therapeutics targeting CB1 has been consistently hindered ...The cannabinoid receptor 1 (CB1) has emerged as a promising candidate for next-generation non-opioid therapies. However, the development of therapeutics targeting CB1 has been consistently hindered by significant adverse effects. Here, through structure-activity relationship analyses focused on biased signaling, we rationally design two G-biased CB1 agonists, LZD503 and LZD505. Our design strategy employed structural spatial tuning of the agonist scaffold to disrupt specific molecular interactions and minimize steric conflicts with critical tip residues within the ligand-binding pocket, thereby promoting preferential G-pathway signaling. Cryo-electron microscopy structures of the CB1-G-protein complexes bound to these designed agonists confirmed that their anticipated conformational poses favored G-biased signaling. Both designed compounds demonstrated promising results by alleviating pain and mitigating unwanted responses in mice. The elucidated CB1 complex structures and the resulting insights establish a comprehensive framework for the structure-guided development of innovative CB1-targeted analgesics with reduced adverse effect profiles.
History
DepositionFeb 7, 2026Deposition site: PDBJ / Processing site: PDBC
Revision 1.0May 20, 2026Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0May 20, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Jun 10, 2026Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first / _em_admin.last_update
Revision 1.1Jun 10, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / Category: citation / em_admin / Data content type: EM metadata / EM metadata / EM metadata
Item: _citation.journal_volume / _citation.page_first / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
R: Cannabinoid receptor 1
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
S: Scfv16
hetero molecules


Theoretical massNumber of molelcules
Total (without water)169,1696
Polymers168,7845
Non-polymers3851
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#2: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 40414.047 Da / Num. of mol.: 1 / Mutation: S47N,G203A,E245A,A326S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P63096, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37285.734 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
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7861.143 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

-
Protein / Antibody / Non-polymers , 3 types, 3 molecules RS

#1: Protein Cannabinoid receptor 1 / CB-R / CB1 / CANN6


Mass: 56612.051 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CNR1, CNR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P21554
#5: Antibody Scfv16


Mass: 26610.615 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera frugiperda (fall armyworm)
#6: Chemical ChemComp-A1E5T / methyl (2~{S},3~{R})-2-[[1-[(4-fluorophenyl)methyl]indazol-3-yl]carbonylamino]-3-oxidanyl-butanoate


Mass: 385.389 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H20FN3O4 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Cannabinoid receptor 1 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1-#5 / Source: RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo sapiens (human)9606
31Mus musculus (house mouse)10090
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 700 nm / Cs: 2.7 mm
Image recordingElectron dose: 52 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

EM software
IDNameVersionCategory
1RELION4particle selection
2PHENIX1.19.2_4158model refinement
13RELION43D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.42 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 231363 / Symmetry type: POINT
RefinementHighest resolution: 2.42 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0038847
ELECTRON MICROSCOPYf_angle_d0.64912011
ELECTRON MICROSCOPYf_dihedral_angle_d4.7841220
ELECTRON MICROSCOPYf_chiral_restr0.0431393
ELECTRON MICROSCOPYf_plane_restr0.0041516

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more