[English] 日本語
Yorodumi
- PDB-6k42: cryo-EM structure of alpha2BAR-Gi1 complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6k42
Titlecryo-EM structure of alpha2BAR-Gi1 complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Alpha-2A adrenergic receptor,Endolysin,Alpha-2B adrenergic receptor,Alpha-2B adrenergic receptor
  • scFvSingle-chain variable fragment
KeywordsMEMBRANE PROTEIN / GPCR / Complex / cryo-EM
Function / homology
Function and homology information


Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / regulation of vascular associated smooth muscle contraction / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / G beta:gamma signalling through PLC beta ...Activation of the phototransduction cascade / Sensory perception of sweet, bitter, and umami (glutamate) taste / regulation of vascular associated smooth muscle contraction / Olfactory Signaling Pathway / negative regulation of uterine smooth muscle contraction / adenylate cyclase-inhibiting adrenergic receptor signaling pathway / phospholipase C-activating adrenergic receptor signaling pathway / alpha2-adrenergic receptor activity / Adrenaline signalling through Alpha-2 adrenergic receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / alpha-2C adrenergic receptor binding / receptor transactivation / epinephrine binding / Prostacyclin signalling through prostacyclin receptor / G alpha (z) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G beta:gamma signalling through BTK / Adenylate cyclase inhibitory pathway / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / alpha-1B adrenergic receptor binding / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / positive regulation of uterine smooth muscle contraction / Thromboxane signalling through TP receptor / negative regulation of norepinephrine secretion / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Ca2+ pathway / G alpha (s) signalling events / negative regulation of calcium ion transmembrane transporter activity / negative regulation of epinephrine secretion / G alpha (q) signalling events / Extra-nuclear estrogen signaling / G alpha (12/13) signalling events / heterotrimeric G-protein binding / dopaminergic synapse / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (i) signalling events / GPER1 signaling / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / negative regulation of calcium ion-dependent exocytosis / ADP signalling through P2Y purinoceptor 1 / thermoception / phototransduction, visible light / Surfactant metabolism / positive regulation of potassium ion transport / positive regulation of blood pressure / fear response / positive regulation of membrane protein ectodomain proteolysis / thioesterase binding / negative regulation of insulin secretion involved in cellular response to glucose stimulus / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / norepinephrine binding / Adrenoceptors / intestinal absorption / Extra-nuclear estrogen signaling / positive regulation of epidermal growth factor receptor signaling pathway / photoreceptor outer segment membrane / G alpha (i) signalling events / spectrin binding / positive regulation of wound healing / adrenergic receptor signaling pathway / activation of protein kinase activity / Rho protein signal transduction / negative regulation of calcium ion transport / regulation of vasoconstriction / photoreceptor outer segment / GABA-ergic synapse / positive regulation of protein localization to cell cortex / negative regulation of insulin secretion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / negative regulation of lipid catabolic process / adenylate cyclase-activating adrenergic receptor signaling pathway / presynaptic active zone membrane / regulation of mitotic spindle organization / cellular response to forskolin / cellular response to hormone stimulus / viral release from host cell by cytolysis / cardiac muscle cell apoptotic process / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of neuron differentiation / photoreceptor inner segment / presynaptic modulation of chemical synaptic transmission / activation of protein kinase B activity / peptidoglycan catabolic process / G protein-coupled receptor binding / female pregnancy / G protein-coupled receptor activity / positive regulation of cytokine production
Similarity search - Function
Alpha 2B adrenoceptor / Alpha 2A adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group I / Endolysin T4 type / T4-type lysozyme / Glycoside hydrolase, family 24 / Lysozyme domain superfamily / Phage lysozyme / Serpentine type 7TM GPCR chemoreceptor Srsx ...Alpha 2B adrenoceptor / Alpha 2A adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group I / Endolysin T4 type / T4-type lysozyme / Glycoside hydrolase, family 24 / Lysozyme domain superfamily / Phage lysozyme / Serpentine type 7TM GPCR chemoreceptor Srsx / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / 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) / Lysozyme-like domain superfamily / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Chem-CZX / Endolysin / Alpha-2A adrenergic receptor / Alpha-2B adrenergic 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 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesBos taurus (cattle)
Mus musculus (house mouse)
Homo sapiens (human)
Enterobacteria phage RB59 (virus)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å
AuthorsYuan, D. / Liu, Z. / Wang, H.W. / Kobilka, B.K.
CitationJournal: Nat Chem Biol / Year: 2020
Title: Activation of the α adrenoceptor by the sedative sympatholytic dexmedetomidine.
Authors: Daopeng Yuan / Zhongmin Liu / Jonas Kaindl / Shoji Maeda / Jiawei Zhao / Xiaoou Sun / Jun Xu / Peter Gmeiner / Hong-Wei Wang / Brian K Kobilka /
Abstract: The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in ...The α adrenergic receptors (αARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. αARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective αAR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective αAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to βAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the αAR in complex with dexmedetomidine and Go at a resolution of 2.9 Å by single-particle cryo-EM. The structure reveals the mechanism of αAR-selective activation and provides insights into Gi/o coupling specificity.
History
DepositionMay 23, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Apr 15, 2020Provider: repository / Type: Initial release
Revision 1.1May 6, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2May 13, 2020Group: Structure summary / Category: audit_author / Item: _audit_author.name

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-9912
  • 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
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
R: Alpha-2A adrenergic receptor,Endolysin,Alpha-2B adrenergic receptor,Alpha-2B adrenergic receptor
H: scFv
hetero molecules


Theoretical massNumber of molelcules
Total (without water)178,0626
Polymers177,8625
Non-polymers2001
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area10910 Å2
ΔGint-57 kcal/mol
Surface area54780 Å2

-
Components

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

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


Mass: 40415.031 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: GNAI1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P63097
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 38530.992 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Gnb1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P62874
#3: 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 (butterflies/moths) / References: UniProt: P59768

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

#4: Protein Alpha-2A adrenergic receptor,Endolysin,Alpha-2B adrenergic receptor,Alpha-2B adrenergic receptor / Alpha-2 adrenergic receptor subtype C10 / Alpha-2A adrenoreceptor / Alpha-2AAR / Lysis protein / ...Alpha-2 adrenergic receptor subtype C10 / Alpha-2A adrenoreceptor / Alpha-2AAR / Lysis protein / Lysozyme / Muramidase / Alpha-2 adrenergic receptor subtype C2 / Alpha-2B adrenoreceptor / Alpha-2BAR / Alpha-2 adrenergic receptor subtype C2 / Alpha-2B adrenoreceptor / Alpha-2BAR


Mass: 58156.211 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Enterobacteria phage RB59 (virus)
Gene: ADRA2A, ADRA2R, ADRAR, e, RB59_126, ADRA2B, ADRA2L1, ADRA2RL1
Production host: Spodoptera (butterflies/moths)
References: UniProt: P08913, UniProt: A0A097J809, UniProt: P18089, lysozyme
#5: Antibody scFv / Single-chain variable fragment


Mass: 32898.781 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Spodoptera (butterflies/moths)
#6: Chemical ChemComp-CZX / 4-[(1~{S})-1-(2,3-dimethylphenyl)ethyl]-1~{H}-imidazole / Dexmedetomidine


Mass: 200.280 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H16N2 / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: alpha2BAR-Gi1 complex / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES
Molecular weightValue: 0.15 MDa / Experimental value: YES
Source (natural)Organism: Spodoptera (butterflies/moths)
Buffer solutionpH: 7.5
SpecimenConc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 %

-
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: SPOT SCAN
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.13_2998: / Classification: refinement
CTF correctionType: NONE
3D reconstructionResolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 235982 / Symmetry type: POINT

+
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