Structural mechanisms of potent lysophosphatidic acid receptor 1 activation by nonlipid basic agonists.

ABSTRACT: Lysophosphatidic acid receptor 1 (LPA₁) is one of the G protein-coupled receptors activated by the lipid mediator, lysophosphatidic acid (LPA). LPA₁ is associated with a variety of diseases, and LPA₁ agonists have potential therapeutic value for treating obesity and depression. Although potent nonlipid LPA₁ agonists have recently been identified, the mechanisms of nonlipid molecule-mediated LPA₁ activation remain unclear. Here, we report a cryo-electron microscopy structure of the human LPA₁-G_i complex bound to a nonlipid basic agonist, CpY, which has 30-fold higher agonistic activity as compared with LPA. Structural comparisons of LPA₁ with other lipid GPCRs revealed that the negative charge in the cha

SUBMITTER: Akasaka H 

PROVIDER: S-EPMC11541586 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature