Fig. 1.

PAC1 receptor ensemble of open (G4) and closed (G1–G3) states. (A) Diagram of PAC1R conformational transition by the Markov state model and transition path theory. Vector diagrams (N-to-C of helix 1 in ECD) show the ECD orientations. The ECD N-terminal is show in purple. (B) The “zipper” between residues 80–91 and ECL3 in the open state. Key polar and hydrophobic side chains are shown in sticks and spheres, respectively. (C) Interactions between PACAP1–38 and PAC1R in ECD-open conformation. The sphere indicates the N-terminus of the PACAP peptide. Reprinted with permission from Liao et al. (2017) Sci Rep 7 (1):5427