Fig. 1: Conformational states and N-C rotation angles of arrestin-3 complexes revealed by MD simulations.

A Residue positions K313 and G317 at the termini of the back loop (blue), and D291 and H296 for gate loop (pink) are shown on the 3D structure of arrestin-3 (PDB ID: 3P2D)²⁸ together with the residues of the polar core (green) and three-element region (yellow) as well as inter-domain aromatic core (purple). B Distribution of the distances used to identify the conformational state of the gate loop and the back loop in arrestin-3 trajectories and those measured in active/pre-activated and inactive structures of arrestins (See Supplementary Table 1 for the complete list of structures). Values for inactive and receptor-bound structures are shown in red and green dots, respectively. Notably, inositol hexakisphosphate-bound arrestin-3 (PDB ID:5TV1)¹⁶ adopts an extremely long distance (See green dot outlier) at the gate loop, due to the perturbation induced by the IP6 molecule near the polar core. C Superposition of traces of two extreme conformations from the principal component analysis of arrestin-3 structures, aligned on the N terminal domain, showing the rotation axis and direction (See Methods). D Table summarizing the occurrence of rotated states in arrestin-3-compound complexes and the average rotation angle.