Activation Microswitches in Adenosine Receptor A_2A Function as Rheostats in the Cell Membrane.

ABSTRACT: Although multiple components of the cell membrane modulate the stability and activation of G protein-coupled receptors (GPCRs), insights into the dynamics of GPCR structures come from biophysical studies conducted in detergents. This is because of the challenges of studying activation in a multicomponent lipid bilayer. To understand the role of cellular membrane lipids and cations in GPCR activation, we performed multiscale molecular dynamics simulations (56 μs) on three different conformational states of adenosine receptor A_2AR, in both the cell membrane-like lipid bilayer and in detergent micelles. Molecular dynamics (MD) simulations show that the phosphatidylinositol bisphosphate (PIP2) interacts with the basic residues in the intracellular regions of A_2AR, thereby

SUBMITTER: Ma N 

PROVIDER: S-EPMC8526178 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature