Allosteric modulation of the adenosine A_2A receptor by cholesterol.

ABSTRACT: Cholesterol is a major component of the cell membrane and commonly regulates membrane protein function. Here, we investigate how cholesterol modulates the conformational equilibria and signaling of the adenosine A_2A receptor (A_2AR) in reconstituted phospholipid nanodiscs. This model system conveniently excludes possible effects arising from cholesterol-induced phase separation or receptor oligomerization and focuses on the question of allostery. GTP hydrolysis assays show that cholesterol weakly enhances the basal signaling of A_2AR while decreasing the agonist EC₅₀. Fluorine nuclear magnetic resonance (¹⁹F NMR) spectroscopy shows that this enhancement arises from an increase in the receptor's active state population and a G-protein-bou

SUBMITTER: Huang SK 

PROVIDER: S-EPMC8730723 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature