24XZ

P2Y14R-Gi complex bound to UDP

Summary for 24XZ

• Entry DOI: 10.2210/pdb24xz/pdb
• EMDB information: 69905
• Descriptor: 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, ... (5 entities in total)
• Functional Keywords: gpcr, nucleotide, g protein, signaling protein
• Biological source: Rattus rattus (black rat); More
• Total number of polymer chains: 5
• Total formula weight: 269218.69

Authors

Oshima, H.S.,Akasaka, H.,Sano, F.K.,Nureki, O. (deposition date: 2026-03-24, release date: 2026-06-10)

Primary citation

Oshima, H.S.,Akasaka, H.,Sano, F.K.,Nureki, O.
Structural insights into the ligand and G protein recognition by P2Y 13 R.
Biochem.Biophys.Res.Commun., 827:153976-153976, 2026

PubMed 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 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.

PubMed: 42208230
DOI: 10.1016/j.bbrc.2026.153976

Experimental method

ELECTRON MICROSCOPY (2.93 Å)