[English] 日本語
Yorodumi
- PDB-8wu1: Cryo-EM structure of CB1-beta-arrestin1 complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8wu1
TitleCryo-EM structure of CB1-beta-arrestin1 complex
Components
  • Beta-arrestin-1
  • Cannabinoid receptor 1,Vasopressin V2 receptor
  • Fab30 heavy chain
  • Fab30 light chain
KeywordsMEMBRANE PROTEIN / cannabinoid receptor / arrestin / biased signal / class A GPCR
Function / homology
Function and homology information


TGFBR3 regulates TGF-beta signaling / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / MAP2K and MAPK activation / Activation of SMO / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / cannabinoid signaling pathway / regulation of penile erection ...TGFBR3 regulates TGF-beta signaling / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / MAP2K and MAPK activation / Activation of SMO / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / cannabinoid signaling pathway / regulation of penile erection / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / negative regulation of dopamine secretion / retrograde trans-synaptic signaling by endocannabinoid / cannabinoid receptor activity / negative regulation of mast cell activation / AP-2 adaptor complex binding / Ub-specific processing proteases / negative regulation of fatty acid beta-oxidation / clathrin coat of coated pit / clathrin heavy chain binding / negative regulation of serotonin secretion / positive regulation of acute inflammatory response to antigenic stimulus / regulation of feeding behavior / Cargo recognition for clathrin-mediated endocytosis / hemostasis / desensitization of G protein-coupled receptor signaling pathway / telencephalon development / regulation of presynaptic cytosolic calcium ion concentration / negative regulation of action potential / Clathrin-mediated endocytosis / clathrin-dependent endocytosis / positive regulation of blood pressure / positive regulation of fever generation / Class A/1 (Rhodopsin-like receptors) / G protein-coupled receptor internalization / acetylcholine receptor binding / inositol hexakisphosphate binding / axonal fasciculation / regulation of metabolic process / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (s) signalling events / clathrin binding / regulation of synaptic transmission, GABAergic / small molecule binding / positive regulation of systemic arterial blood pressure / pseudopodium / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of intracellular signal transduction / positive regulation of receptor internalization / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / endocytic vesicle / negative regulation of Notch signaling pathway / maternal process involved in female pregnancy / cellular response to hormone stimulus / regulation of synaptic transmission, glutamatergic / activation of adenylate cyclase activity / negative regulation of blood pressure / positive regulation of vasoconstriction / response to nutrient / response to cytokine / regulation of insulin secretion / GABA-ergic synapse / response to nicotine / response to cocaine / G protein-coupled receptor binding / clathrin-coated endocytic vesicle membrane / G protein-coupled receptor activity / positive regulation of neuron projection development / receptor internalization / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / memory / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Vasopressin regulates renal water homeostasis via Aquaporins / glucose homeostasis / protein transport / Cargo recognition for clathrin-mediated endocytosis / actin cytoskeleton / Clathrin-mediated endocytosis / positive regulation of protein phosphorylation / presynaptic membrane / growth cone / ubiquitin-dependent protein catabolic process / cytoplasmic vesicle / G alpha (i) signalling events / G alpha (s) signalling events / spermatogenesis / molecular adaptor activity / response to lipopolysaccharide / response to ethanol / mitochondrial outer membrane / positive regulation of ERK1 and ERK2 cascade / endosome / G protein-coupled receptor signaling pathway / positive regulation of apoptotic process / membrane raft / negative regulation of cell population proliferation / positive regulation of cell population proliferation / positive regulation of gene expression / perinuclear region of cytoplasm
Similarity search - Function
Vasopressin V2 receptor / Vasopressin receptor / Cannabinoid receptor type 1 / Cannabinoid receptor family / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain ...Vasopressin V2 receptor / Vasopressin receptor / Cannabinoid receptor type 1 / Cannabinoid receptor family / Arrestin, conserved site / Arrestins signature. / Arrestin / Arrestin, N-terminal / Arrestin-like, N-terminal / Arrestin C-terminal-like domain / Arrestin (or S-antigen), N-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin (or S-antigen), C-terminal domain / Arrestin-like, C-terminal / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / Immunoglobulin E-set
Similarity search - Domain/homology
Chem-KCA / Beta-arrestin-1 / Cannabinoid receptor 1 / Vasopressin V2 receptor
Similarity search - Component
Biological speciesBos taurus (domestic cattle)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsLiao, Y. / Zhang, H. / Shen, Q. / Cai, C.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Cell / Year: 2023
Title: Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism.
Authors: Yu-Ying Liao / Huibing Zhang / Qingya Shen / Chenxi Cai / Yu Ding / Dan-Dan Shen / Jia Guo / Jiao Qin / Yingjun Dong / Yan Zhang / Xiao-Ming Li /
Abstract: Cannabis activates the cannabinoid receptor 1 (CB1), which elicits analgesic and emotion regulation benefits, along with adverse effects, via G and β-arrestin signaling pathways. However, the lack ...Cannabis activates the cannabinoid receptor 1 (CB1), which elicits analgesic and emotion regulation benefits, along with adverse effects, via G and β-arrestin signaling pathways. However, the lack of understanding of the mechanism of β-arrestin-1 (βarr1) coupling and signaling bias has hindered drug development targeting CB1. Here, we present the high-resolution cryo-electron microscopy structure of CB1-βarr1 complex bound to the synthetic cannabinoid MDMB-Fubinaca (FUB), revealing notable differences in the transducer pocket and ligand-binding site compared with the G protein complex. βarr1 occupies a wider transducer pocket promoting substantial outward movement of the TM6 and distinctive twin toggle switch rearrangements, whereas FUB adopts a different pose, inserting more deeply than the G-coupled state, suggesting the allosteric correlation between the orthosteric binding pocket and the partner protein site. Taken together, our findings unravel the molecular mechanism of signaling bias toward CB1, facilitating the development of CB1 agonists.
History
DepositionOct 19, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Mar 20, 2024Provider: repository / Type: Initial release
Revision 1.1Oct 2, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.journal_abbrev / _citation.journal_id_CSD ..._citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 1.2Oct 16, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Beta-arrestin-1
H: Fab30 heavy chain
L: Fab30 light chain
R: Cannabinoid receptor 1,Vasopressin V2 receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)143,9285
Polymers143,5314
Non-polymers3971
Water00
1


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

-
Components

#1: Protein Beta-arrestin-1


Mass: 44135.273 Da / Num. of mol.: 1 / Mutation: R169E, I386A, V387A, F388A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (domestic cattle) / Gene: ARRB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P17870
#2: Antibody Fab30 heavy chain


Mass: 25650.502 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli BL21(DE3) (bacteria)
#3: Antibody Fab30 light chain


Mass: 23435.064 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli BL21(DE3) (bacteria)
#4: Protein Cannabinoid receptor 1,Vasopressin V2 receptor


Mass: 50310.129 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CNR1, AVPR2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P21554, UniProt: P30518
#5: Chemical ChemComp-KCA / methyl N-{1-[(4-fluorophenyl)methyl]-1H-indazole-3-carbonyl}-3-methyl-L-valinate


Mass: 397.443 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H24FN3O3 / Comment: agonist*YM
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Cryo-EM structure of human cannabinoid receptor 1 with effector protein
Type: COMPLEX
Details: MDMB-Fubinaca, cannabinoid receptor 1, arrestin2, Fab30
Entity ID: #1-#4 / Source: RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
11Bos taurus (domestic cattle)9913
21Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
11Spodoptera frugiperda (fall armyworm)7108
21Escherichia coli BL21(DE3) (bacteria)469008
Buffer solutionpH: 7.5
SpecimenConc.: 5 mg/ml / Embedding 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: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 52 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 110196 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0047437
ELECTRON MICROSCOPYf_angle_d0.85810216
ELECTRON MICROSCOPYf_dihedral_angle_d4.1874360
ELECTRON MICROSCOPYf_chiral_restr0.0411245
ELECTRON MICROSCOPYf_plane_restr0.0041267

+
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