Docking model of initial interaction of Gβγ with rhodopsin. (A) Cryo-EM structure of rhodopsin (reddish-purple) bound to a heterotrimeric G protein from Tsai et al. (2019; PDB accession no. 6QNO) composed of Gi1 α (Ras domain in yellow), Gβ1 (blue), and Gγ1 (bluish-green). (B) Initial docking model showing possible orientations of Gβγ from the GRK-Gβ1γ2 structure (PDB accession no. 1OMW), with respect to ground state of rhodopsin (grey; PDB accession no. 1U19), which was aligned with the G-protein-bound state of rhodopsin in A using PyMOL. The Gβγ from the GRK-Gβ1γ2 structure was used since much of the Gγ2 C-terminus is resolved (Lodowski et al., 2003). Gβγ from A is shown in grey for reference and Gi1 α from A is removed for clarity. There is not enough information to know the exact location of a Gβγ docking conformation, resulting in an approximate manual docking of Gβγ in a position similar to Gi1 α in A that would allow interactions between the C-terminus of Gγ and rhodopsin. (C) View of bond between Tyr7.53 and Phe8.50 in ground state rhodopsin (PDB accession no. 1U19) that is a hallmark of an inactive GPCR. (D) View of separation of Tyr7.53 and Phe8.50 in rhodopsin bound to Gi1 (PDB accession no. 6QNO).