Mechanism of allosteric regulation of β₂-adrenergic receptor by cholesterol.

ABSTRACT: There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. However, there are no data showing how exactly the regulation emerges from specific lipid-protein interactions. Here we show in atomistic detail how the human β₂-adrenergic receptor (β₂AR) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β₂AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located near the transmembrane helices 5-7 of the receptor. The alternative mechanism, where the β₂AR conformation would be modulated by membrane-mediated

SUBMITTER: Manna M 

PROVIDER: S-EPMC5182060 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature