Figure 11.
Reorganization of the extracellular surface of the GLP-1R is critical to propagation of signaling. Amino acids involved in efficacy across cAMP (upper panels), [Ca2+]i (middle panels), and pERK (lower panels) for GLP-1 (left-hand panels) and exendin-4 (right-hand panels) were mapped onto the inactive GLP-1R model and the fully active exendin-P5 (ExP5)-bound GLP-1R structure. Displayed in surface representation are mutated amino acids that affect efficacy: yellow (2–5-fold reduction in affinity); light orange (5–10-fold reduction in affinity); red (>30-fold reduction in affinity); or green (increased affinity). Mutated residues not affected are displayed as gray (inactive receptor) or blue (active receptor).