Supplementary Figure 2: Analysis of arrestin subtypes with focus on β-arrestins.

a, Clustering arrestin structures by residue contact fingerprints separates active and inactive arrestins. Within the cluster of inactive state structures, the method clearly distinguishes between visual and β-arrestins, and within the subcluster of visual arrestins separates rod and cone arrestins. Extracting the features (contacts) that determine the clustering pattern enables the analysis of differences between visual and β-arrestins. b, Contacts that are only present in β-arrestins and absent from visual arrestins (see the Methods for details). c, Contacts shown in b plotted on the structure (PDB 1G4R, chain A). Most of the contacts unique to β-arrestins seem to occur in the C domain. For instance, there seems to be a group of contacts stabilizing the distal part of the body of the C domain. d, Sequence analysis showing that the most variable region (sequence-wise) between visual and β-arrestins is the region surrounding the C-loop (C.s15s16). Given that this loop is known to interact with transmembrane helix 4 of the receptor, it is possible that the sequence differences identified here might be important in determining the differences in receptor selectivity across different arrestin subtypes.