Figure 3.

Structural determinants on Gβγ that govern modulation of Ca_V2 channels. (A, B) Ribbon diagram renderings of the heterotrimeric G protein structure in panel A, and the Gβγ dimer in panel B (Gα_i - green; Gβ₁ - red; and Gγ₂ blue). Gβ adopts a seven blade β-propeller structure with an α-helical N-terminal domain that binds to the α-helical N-terminus of Gγ. Gα interacts with multiple residues on the top face of Gβ and the side aspect of propeller blade 1. Many effectors bind to a protein interaction “hot spot” on the surface of Gβ that is masked by Gα in the heterotrimer. (C, D) Molecular surface rendering of the Gβγ dimer (Gβ - red; Gγ - blue). Panel C shows the Gα interacting face of Gβγ, and panel D is rotated ~180° to show opposite face of Gβγ. Residues marked in yellow have been reported to disrupt inhibition of Ca_V2 channels. Residues marked in green are involved in crosstalk between Gβ1 and PKC phosphorylation of Ca_V2.2. Molecular graphics images based on data reported by Wall et al [144] (PDB ID: 1GP2) were produced using the UCSF Chimera package [256, 257] from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco.