Fig. 2|. The receptor core favours arrestin activation through interactions mediated by the receptor’s intracellular loops.

a, The core interface. b, The conformation of the finger loop is largely determined by the presence or absence of a receptor, with little coupling to the arrestin activation state. In simulations of arrestin-1 bound to the receptor core, the finger loop retains a helical conformation (blue). Upon removal of the core but in the presence of the R_P tail, the finger loop collapses towards a set of disordered states (magenta), even as the global arrestin conformation remains active. This ensemble more closely resembles that observed in simulations starting from the inactive state (grey). c, Pulling the finger loop to its receptor-bound (helical) conformation does not induce twist angles characteristic of active states. d, In simulations in which the C loop is pushed away from the middle loop of the N domain, mimicking IL2 binding, arrestin adopts active conformations (six independent simulations for each condition; P = 0.002, two-sided t-test, when compared to unbiased simulations; and P = 0.0004 when compared to simulations in which the finger loop is pulled to its active state; see Methods). See Extended Data Fig. 4 for all TMD traces.