¹⁹F-NMR studies of the impact of different detergents and nanodiscs on the A_2A adenosine receptor

Abstract

For the A_2A adenosine receptor (A_2AAR), a class A G-protein-coupled receptor (GPCR), reconstituted in n-dodecyl-β-D-maltoside (DDM)/cholesteryl hemisuccinate (CHS) mixed micelles, previous ¹⁹F-NMR studies revealed the presence of multiple simultaneously populated conformational states. Here, we study the influence of a different detergent, lauryl maltose neopentyl glycol (LMNG) in mixed micelles with CHS, and of lipid bilayer nanodiscs on these conformational equilibria. The populations of locally different substates are pronouncedly different in DDM/CHS and LMNG/CHS micelles, whereas the A_2AAR conformational manifold in LMNG/CHS micelles is closely similar to that in the lipid bilayer nanodiscs. Considering that nanodiscs represent a closer match of the natural lipid bilayer membrane, these observations support that LMNG/CHS micelles are a good choice for reconstitution trials of class A GPCRs for NMR studies in solution.