Structure of the active G_i-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist.

ABSTRACT: Lysophosphatidic acid receptor 1 (LPA₁) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA₁ is a drug target for various diseases, including cancer, inflammation, and neuropathic pain. Notably, LPA₁ agonists have potential therapeutic value for obesity and urinary incontinence. Here, we report a cryo-electron microscopy structure of the active human LPA₁-G_i complex bound to ONO-0740556, an LPA analog with more potent activity against LPA₁. Our structure elucidated the details of the agonist binding mode and receptor activation mechanism mediated by rearrangements of transmembrane segment 7 and the central hydrophobic core. A structural comparison of LPA₁

SUBMITTER: Akasaka H 

PROVIDER: S-EPMC9477835 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature