[English] 日本語
Yorodumi
- EMDB-33512: Adenosine receptor bound to an agonist in complex with G protein ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-33512
TitleAdenosine receptor bound to an agonist in complex with G protein obtained by cryo-EM
Map data
Sample
  • Complex: Adenosine receptor bound to an agonist in complex with G protein obtained by cryo-EM
    • Complex: G protein
      • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Complex: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT
      • Protein or peptide: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT
  • Ligand: 2-[6-azanyl-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-yl]sulfanylethanamide
KeywordsG protein coupled-receptor / membrane protein
Function / homology
Function and homology information


Adenosine P1 receptors / G protein-coupled adenosine receptor activity / Surfactant metabolism / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / hair follicle placode formation / PKA activation in glucagon signalling / developmental growth / intracellular transport ...Adenosine P1 receptors / G protein-coupled adenosine receptor activity / Surfactant metabolism / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / regulation of skeletal muscle contraction / hair follicle placode formation / PKA activation in glucagon signalling / developmental growth / intracellular transport / D1 dopamine receptor binding / renal water homeostasis / vascular endothelial cell response to laminar fluid shear stress / Hedgehog 'off' state / activation of adenylate cyclase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to acidic pH / presynaptic modulation of chemical synaptic transmission / cellular response to glucagon stimulus / intracellular glucose homeostasis / adenylate cyclase activator activity / trans-Golgi network membrane / positive regulation of insulin secretion involved in cellular response to glucose stimulus / electron transport chain / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / bone development / vasodilation / platelet aggregation / cognition / Schaffer collateral - CA1 synapse / positive regulation of insulin secretion / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / sensory perception of smell / 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 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / 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 / positive regulation of cold-induced thermogenesis / GPER1 signaling / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / extracellular vesicle / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / GTPase binding / G protein activity / Ca2+ pathway / 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 / electron transfer activity / periplasmic space / Extra-nuclear estrogen signaling / iron ion binding / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / heme binding / synapse / GTP binding / protein-containing complex binding / glutamatergic synapse / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol
Similarity search - Function
Adenosine A2B receptor / Adenosine receptor / G-protein alpha subunit, group S / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Serpentine type 7TM GPCR chemoreceptor Srsx / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit ...Adenosine A2B receptor / Adenosine receptor / G-protein alpha subunit, group S / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / 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 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
Soluble cytochrome b562 / Adenosine receptor A2b / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Similarity search - Component
Biological speciesHomo sapiens (human) / Oplophorus gracilirostris (arthropod)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.99 Å
AuthorsZhang JY / Chen Y / Hua T / Song GJ
Funding support China, 2 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32022038 China
National Natural Science Foundation of China (NSFC)31770898 China
CitationJournal: Sci Adv / Year: 2022
Title: Cryo-EM structure of the human adenosine A receptor-G signaling complex.
Authors: Ying Chen / Jinyi Zhang / Yuan Weng / Yueming Xu / Weiqiang Lu / Wei Liu / Mingyao Liu / Tian Hua / Gaojie Song /
Abstract: The human adenosine A receptor (AR) is a class A G protein-coupled receptor that is involved in several major physiological and pathological processes throughout the body. AR recognizes its ligands ...The human adenosine A receptor (AR) is a class A G protein-coupled receptor that is involved in several major physiological and pathological processes throughout the body. AR recognizes its ligands adenosine and NECA with relatively low affinity, but the detailed mechanism for its ligand recognition and signaling is still elusive. Here, we present two structures determined by cryo-electron microscopy of AR bound to its agonists NECA and BAY60-6583, each coupled to an engineered G protein. The structures reveal conserved orthosteric binding pockets with subtle differences, whereas the selectivity or specificity can mainly be attributed to regions extended from the orthosteric pocket. We also found that BAY60-6583 occupies a secondary pocket, where residues V250 and N273 were two key determinants for its selectivity against AR. This study offers a better understanding of ligand selectivity for the adenosine receptor family and provides a structural template for further development of AR ligands for related diseases.
History
DepositionMay 31, 2022-
Header (metadata) releaseMay 3, 2023-
Map releaseMay 3, 2023-
UpdateJul 2, 2025-
Current statusJul 2, 2025Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_33512.png

Downloads & links

-
Map

FileDownload / File: emd_33512.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.96 Å/pix.
x 256 pix.
= 245.76 Å		0.96 Å/pix.
x 256 pix.
= 245.76 Å		0.96 Å/pix.
x 256 pix.
= 245.76 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.96 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.0016722487 - 1.7801168
Average (Standard dev.)0.0011677631 (±0.025449883)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 245.76 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_33512_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_33512_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Adenosine receptor bound to an agonist in complex with G protein ...

EntireName: Adenosine receptor bound to an agonist in complex with G protein obtained by cryo-EM
Components
  • Complex: Adenosine receptor bound to an agonist in complex with G protein obtained by cryo-EM
    • Complex: G protein
      • Protein or peptide: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
    • Complex: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT
      • Protein or peptide: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT
  • Ligand: 2-[6-azanyl-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-yl]sulfanylethanamide

-
Supramolecule #1: Adenosine receptor bound to an agonist in complex with G protein ...

SupramoleculeName: Adenosine receptor bound to an agonist in complex with G protein obtained by cryo-EM
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #2: G protein

SupramoleculeName: G protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3
Source (natural)Organism: Oplophorus gracilirostris (arthropod)

-
Supramolecule #3: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT

SupramoleculeName: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4

-
Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

MacromoleculeName: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 28.146844 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: TVSAEDKAAA ERSKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHGGSGGS GGTSGIFETK FQVDKVNFHM FDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NDFKSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED Y FPEFARYT ...String:
TVSAEDKAAA ERSKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHGGSGGS GGTSGIFETK FQVDKVNFHM FDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NDFKSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED Y FPEFARYT TPEDATPEPG EDPRVTRAKY FIRDEFLRIS TASGDGRHYC YPHFTCAVDT ENARRIFNDC RDIIQRMHLR QY ELL

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

MacromoleculeName: 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
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.728426 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: 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 KIWNGSSGGG GSGGGGSSGV SGWRLFKKIS

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

MacromoleculeName: 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
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.891022 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFGSA GSA

-
Macromolecule #4: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT

MacromoleculeName: Soluble cytochrome b562,Adenosine receptor A2b,LgBiT / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Oplophorus gracilirostris (arthropod)
Molecular weightTheoretical: 69.594055 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DYKDDDDAGR AHHHHHHHHH HADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAALD AQKATPPKLE DKSPDSPEMK DFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR NAYIQKYLEN LYFQSLLETQ DALYVALELV IAALSVAGNV L VCAAVGTA ...String:
DYKDDDDAGR AHHHHHHHHH HADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAALD AQKATPPKLE DKSPDSPEMK DFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR NAYIQKYLEN LYFQSLLETQ DALYVALELV IAALSVAGNV L VCAAVGTA NTLQTPTNYF LVSLAAADVA VGLFAIPFAI TISLGFCTDF YGCLFLACFV LVLTQSSIFS LLAVAVDRYL AI CVPLRYK SLVTGTRARG VIAVLWVLAF GIGLTPFLGW NSKDSATNNC TEPWDGTTNE SCCLVKCLFE NVVPMSYMVY FNF FGCVLP PLLIMLVIYI KIFLVACRQL QRTELMDHSR TTLQREIHAA KSLAMIVGIF ALCWLPVHAV NCVTLFQPAQ GKNK PKWAM NMAILLSHAN SVVNPIVYAY RNRDFRYTFH KIISRYLLCQ ADVKSGNGQA GVQPALGVGL NSMGTLVFTL EDFVG DWEQ TAAYNLDQVL EQGGVSSLLQ NLAVSVTPIQ RIVRSGENAL KIDIHVIIPY EGLSADQMAQ IEEVFKVVYP VDDHHF KVI LPYGTLVIDG VTPNMLNYFG RPYEGIAVFD GKKITVTGTL WNGNKIIDER LITPDGSMLF RVTIN

UniProtKB: Soluble cytochrome b562, Adenosine receptor A2b

-
Macromolecule #5: 2-[6-azanyl-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2...

MacromoleculeName: 2-[6-azanyl-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-yl]sulfanylethanamide
type: ligand / ID: 5 / Number of copies: 1 / Formula: I5D
Molecular weightTheoretical: 379.436 Da
Chemical component information

ChemComp-I5D:
2-[6-azanyl-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-yl]sulfanylethanamide / agonist*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 40 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Specialist opticsEnergy filter - Slit width: 10 eV
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.2 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.99 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 190323
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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