The rhodopsin C-tail as a model for the regulation of GPCR–Gβγ interactions. (A) Structure of the ground state of rhodopsin (PDB accession no. 1U19) emphasizing the interaction between TM1, ICL1, and H8 (reddish-purple), and the C-tail (green). (B) Closeup of A with detail of critical side chains. (C) Interactions of the C-tail of rhodopsin 335–345 with TM1, ICL1, and H8 of rhodopsin; above TM1 and ICL1 and below H8 are graphical representations of the sequence alignment of regions analogous to rhodopsin in Class A GPCRs. Grey boxes indicate residues in rhodopsin that interact with the C-tail; boxes with orange outlines represent residues in rhodopsin that are analogous to residues in the EH₂ domain of Eps15 that interact with the NPF motif. Red connecting lines highlight interactions with residues in the C-tail of rhodopsin that are known to be phosphorylated.