Fig. 4. Basis of peptide hormone specificity.
(A) Pairwise comparison of the LA-PTH bound to PTH1R with GLP-1, Exendin-P5 (ExP5), and CGRP in complex with their corresponding receptors, showing the relative positions of peptide ligands and their receptor ECDs. The RAMP1 component was omitted from the CGRPR figure for clarity. (B) Pairwise comparison of the PTH1R structure with GLP-1R bound to GLP-1, ExP5, and CGRPR, showing the pocket shapes accommodating respective peptide ligands. (C) Sequence alignment of class B GPCR peptide ligands. (D) Pocket size and occupancy of peptide ligands in class B GPCR structures. GLP-1Ra is a GLP-1–bound GLP-1R structure, and GLP-1Rb is an ExP5–bound GLP-1R structure.