[English] 日本語
Yorodumi
- PDB-6vms: Structure of a D2 dopamine receptor-G-protein complex in a lipid ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vms
TitleStructure of a D2 dopamine receptor-G-protein complex in a lipid membrane
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Endolysin,D(2) dopamine receptor,D(2) dopamine receptor
  • scFv16
KeywordsSIGNALING PROTEIN / Dopamine / Dopamine receptor / GPCR / G protein / Parkinson's disease
Function / homology
Function and homology information


negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / regulation of synapse structural plasticity / response to histamine ...negative regulation of dopamine receptor signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / negative regulation of dephosphorylation / negative regulation of circadian sleep/wake cycle, sleep / positive regulation of glial cell-derived neurotrophic factor production / acid secretion / dopamine neurotransmitter receptor activity, coupled via Gi/Go / nervous system process involved in regulation of systemic arterial blood pressure / regulation of synapse structural plasticity / response to histamine / regulation of locomotion involved in locomotory behavior / neuron-neuron synaptic transmission / adenohypophysis development / positive regulation of renal sodium excretion / Extra-nuclear estrogen signaling / negative regulation of cellular response to hypoxia / regulation of potassium ion transport / hyaloid vascular plexus regression / cerebral cortex GABAergic interneuron migration / positive regulation of growth hormone secretion / Adenylate cyclase inhibitory pathway / negative regulation of dopamine secretion / adenylate cyclase-inhibiting dopamine receptor signaling pathway / response to inactivity / Dopamine receptors / orbitofrontal cortex development / negative regulation of neuron migration / regulation of dopamine uptake involved in synaptic transmission / branching morphogenesis of a nerve / dopamine binding / phospholipase C-activating dopamine receptor signaling pathway / heterotrimeric G-protein binding / peristalsis / drinking behavior / G protein-coupled receptor complex / grooming behavior / behavioral response to ethanol / auditory behavior / positive regulation of G protein-coupled receptor signaling pathway / dopaminergic synapse / striatum development / positive regulation of urine volume / negative regulation of adenylate cyclase activity / positive regulation of multicellular organism growth / negative regulation of synaptic transmission / G protein-coupled receptor internalization / negative regulation of synaptic transmission, glutamatergic / GTPase activating protein binding / cellular response to ethanol / non-motile cilium / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / response to iron ion / G alpha (i) signalling events / adult walking behavior / response to morphine / neurotransmitter receptor localization to postsynaptic specialization membrane / arachidonate secretion / ciliary membrane / negative regulation of cytosolic calcium ion concentration / pigmentation / temperature homeostasis / heterocyclic compound binding / positive regulation of neuroblast proliferation / regulation of synaptic transmission, GABAergic / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / positive regulation of cytokinesis / dopamine metabolic process / associative learning / behavioral response to cocaine / positive regulation of receptor internalization / sperm flagellum / response to light stimulus / endocytic vesicle / neuroblast proliferation / G-protein alpha-subunit binding / long-term memory / response to axon injury / negative regulation of protein secretion / lateral plasma membrane / potassium channel regulator activity / postsynaptic modulation of chemical synaptic transmission / prepulse inhibition / negative regulation of insulin secretion / viral release from host cell by cytolysis / positive regulation of protein localization to cell cortex / T cell migration / synapse assembly / regulation of sodium ion transport / D2 dopamine receptor binding / ionotropic glutamate receptor binding / cellular response to retinoic acid / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / negative regulation of blood pressure / axon terminus / release of sequestered calcium ion into cytosol
Similarity search - Function
Dopamine D2 receptor / Dopamine receptor family / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Rhopdopsin 7-helix transmembrane proteins / Rhodopsin 7-helix transmembrane proteins / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 ...Dopamine D2 receptor / Dopamine receptor family / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Rhopdopsin 7-helix transmembrane proteins / Rhodopsin 7-helix transmembrane proteins / Endolysin T4 type / T4-type lysozyme / : / Glycoside hydrolase, family 24 / Phage lysozyme / Lysozyme domain superfamily / G-protein alpha subunit, group I / YVTN repeat-like/Quinoprotein amine dehydrogenase / Serpentine type 7TM GPCR chemoreceptor Srsx / 7 Propeller / Methylamine Dehydrogenase; Chain H / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / Few Secondary Structures / Irregular / 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 / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / Lysozyme-like domain superfamily / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / 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 / Up-down Bundle / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
bromoergocryptine / Endolysin / Guanine nucleotide-binding protein G(i) subunit alpha-1 / D(2) dopamine receptor / 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
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Homo sapiens (human)
Enterobacteria phage T4 (virus)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsYin, J. / Chen, K.M. / Clark, M.J. / Hijazi, M. / Kumari, P. / Bai, X. / Sunahara, R.K. / Barth, P. / Rosenbaum, D.M.
Funding support United States, 1items
OrganizationGrant numberCountry
Welch FoundationI-1770 United States
CitationJournal: Nature / Year: 2020
Title: Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane.
Authors: Jie Yin / Kuang-Yui M Chen / Mary J Clark / Mahdi Hijazi / Punita Kumari / Xiao-Chen Bai / Roger K Sunahara / Patrick Barth / Daniel M Rosenbaum /
Abstract: The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such ...The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease and antipsychotic drugs. DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine, leading to stimulation of G and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular G-binding site. The DRD2-G structure represents, to our knowledge, the first experimental model of a G-protein-coupled receptor-G-protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine side chains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help to inform the design of subtype-selective DRD2 ligands for multiple human central nervous system disorders.
History
DepositionJan 28, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 17, 2020Provider: repository / Type: Initial release
Revision 1.1Jun 24, 2020Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title ..._citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Aug 19, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 23, 2024Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / em_admin / pdbx_entry_details / pdbx_initial_refinement_model / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type / _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-21243
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-21243
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
C: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
E: scFv16
R: Endolysin,D(2) dopamine receptor,D(2) dopamine receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)166,7606
Polymers166,1055
Non-polymers6551
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration, SDS PAGE gel electrophoresis
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

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

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


Mass: 40382.047 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnai1, Gnai-1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P10824
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


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 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 9137.474 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 ER

#4: Antibody scFv16


Mass: 27784.896 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)
#5: Protein Endolysin,D(2) dopamine receptor,D(2) dopamine receptor / Lysis protein / Lysozyme / Muramidase / Dopamine D2 receptor / Dopamine D2 receptor


Mass: 51384.059 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Enterobacteria phage T4 (virus), (gene. exp.) Homo sapiens (human)
Gene: e, T4Tp126, DRD2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: D9IEF7, UniProt: P14416, lysozyme
#6: Chemical ChemComp-08Y / bromoergocryptine / bromocriptine


Mass: 654.594 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H40BrN5O5 / Feature type: SUBJECT OF INVESTIGATION / Comment: agonist*YM

-
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: D2 dopamine receptor-G protein complex / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.4
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: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 64 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM software
IDNameVersionCategory
4RELIONCTF correction
7UCSF Chimeramodel fitting
9RELION3.0.1initial Euler assignment
10RELION3.0.1final Euler assignment
11RELION3.0.1classification
12RELION3.0.13D reconstruction
13PHENIXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 783984 / Symmetry type: POINT
Atomic model buildingPDB-ID: 6DDE

6dde


Accession code: 6DDE / Source name: PDB / Type: experimental model

+
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