Figure 5. Model of GCGR bound to glucagon.

a, and b, GCGR with the ECD (magenta) and 7TM domain (blue) bound to glucagon (green). Residues 122–126 and 199–218 (brown) are not defined in the GCGR ECD (GCGR-linker) (PDB 4ERS) and 7TM domain (ECL1) crystal structures, respectively. The GCGR ECD structure and the interactions between GCGR ECD and glucagon resemble those in the GCGR ECD (PDB 4ERS)⁶ and GLP1-GLP1R ECD complex (PDB 3IOL)⁸ structures, respectively. c, and d, The effects of mutation studies of individual GCGR residues on glucagon (green) binding mapped onto the GCGR binding surface using the color coding presented in Figure 4. Important glucagon residues are labeled black. GCGR residues proposed to be important in stabilizing extracellular loops are boxed. GCGR-glucagon residue pairs that are homologous to residue pairs identified in GLP1R-GLP1 cross-linking studies are underlined¹².