Identification of Two New Cholesterol Interaction Sites on the A_2A Adenosine Receptor.

ABSTRACT: By mole, cholesterol is the most abundant component of animal cell plasma membranes. Many membrane proteins have been shown to be functionally dependent on cholesterol, several of which have also been shown to bind cholesterol at well-defined locations on their membrane-facing surface. In this work, a combination of coarse-grained "Martini" and all-atom simulations are used to identify two, to our knowledge, new cholesterol-binding sites on the A_2A adenosine receptor, a G-protein-coupled receptor that is a target for the treatment of Parkinson's disease. One of the sites is also observed to bind cholesterol in several recent, high-resolution crystal structures of the protein, and in the simulations, interacts with cholesterol only when bound to the inverse agonist ZM241385. Cata

SUBMITTER: Rouviere E 

PROVIDER: S-EPMC5738547 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature