Insights into adenosine A2A receptor activation through cooperative modulation of agonist and allosteric lipid interactions
Fig 3
Stabilization of the inactive conformation of apo A2aR in DOPC membrane.
A) Superposition of the inactive-state crystal structure of A2aR (PDB entry: 4EIY, pink) with docked adenosine and an MD-generated apo conformation achieved within a DOPC membrane (magenta, belonging to replica #2 from 1.7 μs) showing B) and C) selected residues delineating the orthosteric pocket. ECL2 and TM helices are labelled where applicable. D) Fluctuation of the distance between TM3-TM7 (from Cα atoms of R1023.50 and Y2887.53, respectively) during MD simulations, starting from the inactive crystal structure (PDB entry: 4EIY). E) Fluctuation of the distance between TM3-TM6 (from Cα atoms of R1023.50 and E2286.30, respectively). F) and G) Vertical movement of ECL2 and TM3, respectively. MD simulations are performed in quadruplicate. Corresponding flat-lines are included to show the observed distance in the active (PDB entry: 6GDG) and inactive (PDB entry: 4EIY) A2aR crystal structures.