Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2.

ABSTRACT: Hydroxycarboxylic acid receptors (HCAR1, HCAR2, and HCAR3) transduce G_i/o signaling upon biding to molecules such as lactic acid, butyric acid and 3-hydroxyoctanoic acid, which are associated with lipolytic and atherogenic activity, and neuroinflammation. Although many reports have elucidated the function of HCAR2 and its potential as a therapeutic target for treating not only dyslipidemia but also neuroimmune disorders such as multiple sclerosis and Parkinson's disease, the structural basis of ligand recognition and ligand-induced G_i-coupling remains unclear. Here we report three cryo-EM structures of the human HCAR2-G_i signaling complex, each bound with different ligands: niacin, acipimox or GSK256073. All three agonists are held in a deep pocket lined by

SUBMITTER: Park JH 

PROVIDER: S-EPMC10628104 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature