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Cholesterol Dependent Activity of the Adenosine A 2A Receptor Is Modulated via the Cholesterol Consensus Motif.
- Source :
- Molecules; Jun2022, Vol. 27 Issue 11, p3529-3529, 14p
- Publication Year :
- 2022
-
Abstract
- Background: Membrane cholesterol dysregulation has been shown to alter the activity of the adenosine A<subscript>2A</subscript> receptor (A<subscript>2A</subscript>R), a G protein-coupled receptor, thereby implicating cholesterol levels in diseases such as Alzheimer's and Parkinson's. A limited number of A<subscript>2A</subscript>R 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 A<subscript>2A</subscript>R, 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 A<subscript>2A</subscript>R. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 27
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 157372807
- Full Text :
- https://doi.org/10.3390/molecules27113529