Molecular basis of prostaglandin E₂ reuptake by organic anion transporter PGT.

ABSTRACT: Prostaglandins (PGs) are bioactive lipids that regulate inflammation, reproduction, and vasopermeability. Timely clearance of excessive PGs is critical to prevent potential damages caused by prolonged signalling. The high-affinity prostaglandin transporter (PGT) plays an essential role in this termination process by efficiently re-uptaking PGs into cells. Here, we report human PGT structures in different oligomerization and substrate-binding states. Beyond the canonical MFS-fold, PGT harbours a cystine-rich extracellular segment that incorporates a Kazal-like domain crucial for PGT localization and activity. Two distinct PGE₂-bound structures revealed essential elements for substrate recognition, elucidating a PGE₂-flipping process during the multi-stop translocation

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC12789631 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature