Figure 12.

Alanine mutation of ECL2 and ECL3 has distinct effects on pERK peptide efficacy for AMY₃R and CTR. Peptide efficacy, derived from operational fitting of concentration–response curves in pERK, are displayed as Δlog τ_c from wild-type for AMY₃R (A–E) and CTR (F–J). Illustrated are top views of the receptors with the extracellular surface subject to alanine scanning depicted (combined surface/cpk representation). Mutations that significantly alter peptide functional log τ_c are colored according to the magnitude of effect, with mutated amino acids without significant alteration to log τ_c colored gray. Amino acid mutations for which there was an insufficiently robust functional effect to quantify by operational modeling are depicted in black. The receptor ECD and peptide are not shown for clarity, with the CTR TM bundle in blue ribbon and RAMP3 in green ribbon in A–E, and CTR TM bundling in red ribbon in F–J. Data for CTR peptide efficacy are from Dal Maso et al., 2018.¹⁷