Figure 7.

Modeling studies. A) Snake-like diagram of Gα₁₃ with the G protein barcode highlighting evolutionary neutral, conserved, and selectivity-determining positions (barcode cutoff 0.96). B) Location of G.H5.23 (cyan) in the receptor-G protein complex (left) and comparison of the α5 helix domain C termini of Gα_s (green) and Gα_i1 (red) (right). Arrows indicate the rotation differences between the α5 helix domains. Comparison of interface contacts and contacting residues between recently published GPCR–G protein structures are shown, as well as for the GPR35 G₁₂/G₁₃ selectivity-determining position G.H5.23. C) Alignment of G.H5.23 contacting receptor residue positions (gray: conserved; yellow: differing). This suggests a structurally yet-to-be-defined, alternative binding mode and contact profile for the G₁₂/G₁₃ family subtypes and their receptor coupling partners.