Structural insight into the self-activation and G-protein coupling of P2Y2 receptor.

ABSTRACT: Purinergic P2Y2 receptor (P2Y2R) represents a typically extracellular ATP and UTP sensor for mediating purinergic signaling. Despite its importance as a pharmacological target, the molecular mechanisms underlying ligand recognition and G-protein coupling have remained elusive due to lack of structural information. In this study, we determined the cryo-electron microscopy (cryo-EM) structures of the apo P2Y2R in complex with G_q, ATP-bound P2Y2R in complex with G_q or G_o, and UTP-bound P2Y4R in complex with G_q. These structures reveal the similarities and distinctions of ligand recognition within the P2Y receptor family. Furthermore, a comprehensive analysis of G-protein coupling reveals that P2Y2R exhibits promiscuity in coupling with both G_q<

SUBMITTER: Lan B 

PROVIDER: S-EPMC12075631 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature