The Lipid Phase Preference of the Adenosine A2a Receptor Depends on Its Ligand Binding State

We formed giant unilamellar protein vesicles (GUPs) out of phase-separating lipid mixtures and incorporated the adenosine 2a receptor (A_2aR) to observe protein portioning between liquid ordered and liquid disordered phases. When no ligand is bound, A_2aR partitions preferentially into the liquid disordered phase of GUPs, while ligand-bound A_2aR partitions into the liquid ordered region. This phenomenon represents a potential allosteric modulation of the protein’s membrane localization, with implications to control signaling pathways via protein segregation within the lipid bilayer.