Structural insights into the activation of the human prostaglandin E₂ receptor EP1 subtype by prostaglandin E₂.

ABSTRACT: Prostaglandin E₂ (PGE₂) mediates diverse physiological processes through four G protein-coupled receptor subtypes (EP1-EP4). While structures of EP2, EP3, and EP4 have been determined, the structural basis for PGE₂ recognition and activation of the EP1 receptor subtype has remained elusive due to its inherent instability. Here, we present the cryoelectron microscopy structure of the human EP1 receptor in complex with PGE₂ and heterotrimeric Gq protein at 2.55 Å resolution, completing the structural characterization of the EP receptor family. Our structure reveals a unique binding mode of PGE₂ within EP1, involving key interactions with residues in the orthosteric pocket. Notably, we observe a less pronounced outward displacement of tra

SUBMITTER: Meng X 

PROVIDER: S-EPMC12107139 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature