Figure 5: ¹⁹F-NMR spectra revealed the different structural states of β-arrestin-1 in response to different phospho-binding patterns.

(a) Common structural changes that occur after β-arrestin-1 activation induced by the binding of functional phosphopeptides. These results suggest the existence of common conformational states representing β-arrestin-1 activation after functional phosphopeptide binding. (b) Specific structural rearrangements after GRK2pp binding. (c) GRK6-encoded specific structural rearrangements at F277 position. (d) V2Rpp specifically stimulated conformational change at Y209 position. (e) Proposed models illustrating the receptor phospho-barcode-encoded distinct arrestin conformations that dictate specific downstream signalling. The phosphorylated C-tail of the receptor (in orange) extends into the cytoplasm. Interaction with the receptor phospho-C-tail induces a structural rearrangement of β-arrestin-1 that includes residues in the finger loop (such as F75) and the middle loop (such as T136); these residues (in purple) might participate in the receptor transmemberane core interaction. Different GRKs encode different conformations in the C-lobe of β-arrestin-1. GRK2 encodes specific conformations of Y249 and L338 (blue triangles), which are recognized by clathrin (in blue). GRK6 encodes distinct β-arrestin-1 conformations, such as the conformation of F277 (red triangle), which might be recognized by signalling proteins such as SRC (in red). Specific V2Rpp-induced conformational change is localized at Y209 (in orange).