GPCR C-tail allosterically modulates Gβγ to facilitate prenyl-GPCR interactions. (A) Rhodopsin (reddish-purple) and the R-state Gβ₁γ₁ (blue) from the rhodopsin–G_i1 structure in Fig. 6 (PDB accession no. 6QNO) with the T-state Gβ₁γ₁ (grey) from the phosducin-Gβγ structure (PDB accession no. 1A0R) superimposed on Gβ₁γ₁ from the rhodopsin–G_i1 structure. (B) Closeup of boxed area in A showing the phosducin bound form of Gβ₁γ₁ (T-state). Distances between residues in the T-state conformation of Gβ₁γ₁ that appear to be too far for the interactions observed in the rhodopsin–G_i1 structure are indicated by dashed red lines. (C) Closeup of boxed area in A showing the rhodopsin bound form of Gβ₁γ₁ (PDB accession no. 6QNO), with atomic distances between the C-tail of rhodopsin and Gβ₁ <4 Å indicated by dashed yellow lines. (D) Rhodopsin and Gβ₁γ₁ from the rhodopsin–G_i1 structure (PDB accession no. 6QNO), emphasizing the location of the farnesyl moiety (red) and the prenyl binding pocket in Gβ₁ in the phosducin Gβγ structure, in relation to the C-tail of rhodopsin. (E) Close-up of boxed area in D showing the cartoon structure and the surface representation of phosducin Gβ₁γ₁ in the T-state, with the surface clipped to emphasize the farnesyl moiety in the prenyl binding pocket. (F) Close-up of boxed area in D showing the cartoon structure and the surface representation of the rhodopsin bound Gβ₁γ₁ from Fig. 6 in the R-state. The farnesyl moiety from the phosducin Gβ₁γ₁ structure is also included to show its relative position and emphasize that the surface representation of R-state of Gβ₁γ₁ is incompatible with prenyl binding, as the pocket is effectively eliminated with the conformational change from the T- to R-state.