Molecular basis for lipid recognition by the prostaglandin D₂ receptor CRTH2.

ABSTRACT: Prostaglandin D₂ (PGD₂) signals through the G protein-coupled receptor (GPCR) CRTH2 to mediate various inflammatory responses. CRTH2 is the only member of the prostanoid receptor family that is phylogenetically distant from others, implying a nonconserved mechanism of lipid action on CRTH2. Here, we report a crystal structure of human CRTH2 bound to a PGD₂ derivative, 15R-methyl-PGD₂ (15mPGD₂), by serial femtosecond crystallography. The structure revealed a "polar group in"-binding mode of 15mPGD₂ contrasting the "polar group out"-binding mode of PGE₂ in its receptor EP3. Structural comparison analysis suggested that these two lipid-binding modes, associated with distinct charge distributions of ligand-binding poc

SUBMITTER: Liu H 

PROVIDER: S-EPMC8364189 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature