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- PDB-24xz: P2Y14R-Gi complex bound to UDP -

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Basic information

Entry
Database: PDB / ID: 24xz
TitleP2Y14R-Gi complex bound to UDP
Components
  • Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
  • Guanine nucleotide-binding protein G(i) subunit alpha-1
  • Soluble cytochrome b562,P2Y purinoceptor 14,LgBiT tag,GFP
  • scFv16
KeywordsSIGNALING PROTEIN / GPCR / Nucleotide / G protein
Function / homology
Function and homology information


G protein-coupled UDP receptor activity / P2Y receptors / G protein-coupled purinergic nucleotide receptor activity / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / hematopoietic stem cell homeostasis / Activation of the phototransduction cascade / Activation of G protein gated Potassium channels / G-protein activation ...G protein-coupled UDP receptor activity / P2Y receptors / G protein-coupled purinergic nucleotide receptor activity / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / hematopoietic stem cell homeostasis / Activation of the phototransduction cascade / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / G alpha (z) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / 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 / bioluminescence / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / generation of precursor metabolites and energy / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / electron transport chain / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / centriolar satellite / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / GDP binding / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / sensory perception of taste / sperm principal piece / adenylate cyclase-activating G protein-coupled receptor signaling pathway / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / G protein activity / midbody / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / periplasmic space / electron transfer activity / Extra-nuclear estrogen signaling / cell population proliferation / ciliary basal body / iron ion binding / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / heme binding / centrosome / synapse / GTP binding / protein-containing complex binding / nucleolus / magnesium ion binding
Similarity search - Function
P2Y14 purinoceptor / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / G-protein alpha subunit, group I / G protein alpha subunit, helical insertion ...P2Y14 purinoceptor / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Green fluorescent protein, GFP / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / G-protein alpha subunit, group I / 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 / 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
URIDINE-5'-DIPHOSPHATE / GFP / Soluble cytochrome b562 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / P2Y purinoceptor 14
Similarity search - Component
Biological speciesRattus rattus (black rat)
Homo sapiens (human)
Escherichia coli (E. coli)
synthetic construct (others)
human respiratory syncytial virus
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.93 Å
AuthorsOshima, H.S. / Akasaka, H. / Sano, F.K. / Nureki, O.
Funding support Japan, 1items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science (JSPS)21H05037 Japan
CitationJournal: Biochem Biophys Res Commun / Year: 2026
Title: Structural insights into the ligand and G protein recognition by P2YR.
Authors: Hidetaka S Oshima / Hiroaki Akasaka / Fumiya K Sano / Osamu Nureki /
Abstract: P2Y purinergic receptors are GPCRs that recognize extracellular nucleotides to mediate diverse physiological processes. Among 12-like subfamily members, P2YR has well-documented roles in ...P2Y purinergic receptors are GPCRs that recognize extracellular nucleotides to mediate diverse physiological processes. Among 12-like subfamily members, P2YR has well-documented roles in neuroprotection and cholesterol metabolism. Notably, P2YR displays robust activity toward the G pathway in addition to its canonical G coupling, yet the structural basis for its ligand recognition and G protein selectivity has remained unclear. Here, we present the cryo-EM structure of the P2YR-G complex bound to ADP at a resolution of 2.83 Å. The structure reveals the distinctive ligand recognition mechanism of P2YR, in which an N-terminal arginine caps the orthosteric binding pocket. Furthermore, we also elucidated the structure of P2YR, which shows the lowest G activation ability among the 12-like P2Y receptors, in complex with UDP and G at a resolution of 2.93 Å. Structural comparison with the 12-like P2Y receptors implicates ICL2-mediated contacts with the Gα hydrophobic cavity as a key structural determinant of G selectivity. Together, these findings provide mechanistic insights into nucleotide signaling and a structural foundation for advancing structure-based approaches to targeting the 12-like P2Y receptors.
History
DepositionMar 24, 2026Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 10, 2026Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jun 10, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

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Assembly

Deposited unit
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(i) subunit alpha-1
R: Soluble cytochrome b562,P2Y purinoceptor 14,LgBiT tag,GFP
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
S: scFv16
hetero molecules


Theoretical massNumber of molelcules
Total (without water)269,2196
Polymers268,8155
Non-polymers4041
Water00
1


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

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Components

#1: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 40586.332 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus rattus (black rat) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62871
#2: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 48846.695 Da / Num. of mol.: 2
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 Soluble cytochrome b562,P2Y purinoceptor 14,LgBiT tag,GFP / Cytochrome b-562 / P2Y14 / G-protein coupled receptor 105 / UDP-glucose receptor


Mass: 102814.008 Da / Num. of mol.: 1 / Mutation: mutation
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human), (gene. exp.) synthetic construct (others), (gene. exp.) human respiratory syncytial virus
Gene: cybC, P2RY14, GPR105, KIAA0001 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P0ABE7, UniProt: Q15391, UniProt: A0A5P9VSM6
#4: Antibody scFv16


Mass: 27720.795 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)
#5: Chemical ChemComp-UDP / URIDINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 404.161 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H14N2O12P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: UDP*YM
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: P2Y13R-Gq complex bound to ADP / Type: COMPLEX / Entity ID: #1, #3, #2, #4 / Source: RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
11Homo sapiens (human)9606
21Rattus rattus (black rat)10117
31Mus musculus (house mouse)10090
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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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: 1600 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 64 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2PHENIX1.19_4092model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 170129 / Symmetry type: POINT

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