Dataset Information
Cholesterol Dependent Activity of the Adenosine A2A Receptor Is Modulated via the Cholesterol Consensus Motif.
Ontology highlight
ABSTRACT: Background
Membrane cholesterol dysregulation has been shown to alter the activity of the adenosine A2A receptor (A2AR), a G protein-coupled receptor, thereby implicating cholesterol levels in diseases such as Alzheimer's and Parkinson's. A limited number of A2AR crystal structures show the receptor interacting with cholesterol, as such molecular simulations are often used to predict cholesterol interaction sites.Methods
Here, we use experimental methods to determine whether a specific interaction between amino acid side chains in the cholesterol consensus motif (CCM) of full length, wild-type human A2AR, and cholesterol modulates activity of the receptor by testing the effects of mutational changes on functional consequences, including ligand binding, G protein coupling, and downstream activation of cyclic AMP.Results and conclusions
Our data, taken with previously published studies, support a model of receptor state-dependent binding between cholesterol and the CCM, whereby cholesterol facilitates both G protein coupling and downstream signaling of A2AR.
SUBMITTER: McGraw C
PROVIDER: S-EPMC9182133 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
Cholesterol Dependent Activity of the Adenosine A<sub>2A</sub> Receptor Is Modulated via the Cholesterol Consensus Motif.
Molecules (Basel, Switzerland) 20220531 11
<h4>Background</h4>Membrane cholesterol dysregulation has been shown to alter the activity of the adenosine A<sub>2A</sub> receptor (A<sub>2A</sub>R), a G protein-coupled receptor, thereby implicating cholesterol levels in diseases such as Alzheimer's and Parkinson's. A limited number of A<sub>2A</sub>R crystal structures show the receptor interacting with cholesterol, as such molecular simulations are often used to predict cholesterol interaction sites.<h4>Methods</h4>Here, we use experimental ...[more]