Figure 6.
Alanine mutation of ECL2 and ECL3 has distinct effects on AMY3R and CTR cAMP functional affinity (log KA). Functional affinities derived from operational fitting of concentration–response curves in cAMP accumulation are displayed as Δlog KA 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 KA are colored according to the magnitude of effect, with mutated amino acids without significant alteration to log KA colored gray. Amino acid mutations where 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 panels A–E, and CTR TM bunding in red ribbon in panels F–J. Data for CTR functional affinity are from Dal Maso et al., 2018.17