CGRPmut and AM occupy similar positions near CLR loops 2, 3, and 4; only their C termini are in proximity to the RAMPs (Figures 1A and 1B). Strikingly, CGRPmut adopts a receptor-bound conformation devoid of secondary structure. Receptor-bound AM lacks secondary structure other than one α-helical turn. Shared turn structures near the peptide C termini similarly position the C-terminal residues adjacent to α2 and the α2-α3 loop of the RAMPs. CGRPmut and AM occupy the same face of the CLR ECD as observed for other class B GPCRs with their positions more similar to that of CRF than PTH (Figure 1C). Helix-breaking Pro residues are prevalent in the CGRP, AM, and AM2 sequences and the four residue segment prior to the C-terminal residue contains turn-favoring Pro or Gly residues, consistent with the observed peptide conformations (Figure 1D). The structures are consistent with our knowledge of the architectures of the intact receptor complexes. The ECDs are oriented such that their C termini could continue toward the membrane with a similar number of residues between the termini visible in the structures and the predicted start of the TM segments (∼17 residues for CLR and ∼8 for the RAMPs). The peptides are oriented such that their N termini containing the receptor-activating regions would be directed toward the 7TM domain.