Fig. 4: Updated action model of the A2AAR.
a A previously proposed three-state action model of the A2AAR and corresponding energy landscapes for the apo and agonist-bound A2AAR68. b Updated scheme of two-dimensional energy landscapes shows long-lived sub-states within inactive-like state with intermediate FRET efficiency (MF) and active-like state with high FRET efficiency (HF). We did not include a state with the lowest FRET efficiency (LF, gray areas) in our updated model, as it was the least populated and assigned to non-functional or improperly folded receptors in the previous study68 and, in the current study, it was not observed as it was indistinguishable from molecules without active acceptor dyes. We updated the estimate of exchange time between MF and HF in apo A2AAR from >2 ms proposed previously68 to >100 ms.
