Fig. 6: Distinct aspects of receptor–β-arrestin2 interactions are differentially influenced by GPCR transmembrane helix-bundles or C-termini.

a Complex configurations for β-arrestins with an adrenergic receptor (β1 adrenergic receptor (b1AR), here exchanged by the aligned structure of active b2AR, PDB: 3SN6) and the V2R (PDB: 7R0C) are shown. Both complex structures feature β-arrestin2 aligned in place of β-arrestin1, while calculated transferability coefficients (see Supplementary Fig. 11 and methods) of β-arrestin2 biosensors in Control cells are projected onto its surface structure (PDB: 3P2D) to indicate the influence of individual GPCR domains on conformational changes (blue indicates helix-bundle transferability of conformational changes, while shades of red indicate C-terminus transferability and biosensors that do not show any transferability are colored in gray). b Calculated transferability coefficients of all β-arrestin2 biosensors in Control cells are shown as bubble plots, also indicating the initial difference in signal between WT GPCRs, shown as the size of the plotted symbols. c, d β-arrestin configurational positioning and tilt angles (with respect to the GPCR alignment axis and plasma membrane) are compared between complexes formed with an adrenergic receptor (orange outline) and the V2R (blue outline). e, f Calculated transferability coefficients are depicted for functional assay data, featuring ERK1/2 activity, β-arrestin2 recruitment, GPCR and β-arrestin2 endosomal delivery, as well as proximal and distal, C-terminal GPCR phosphorylation, in all GRK-specific conditions. These coefficients are shown schematically in (e), and as bubble plots in (f), while the size of the plotted symbols indicates the initial difference in signal between WT GPCRs. Source data are provided as a Source Data file.