Extended Data Figure 8: Interactions between the ECD and stalk/ECL1 in molecular dynamics simulations and comparison with the binding modes of glucagon and mAb1.
From: Structure of the full-length glucagon class B G-protein-coupled receptor
a, Interactions between the ECD and stalk/ECL1 in one typical molecular dynamics simulation snapshot. The residues Y202, K205 and I206 on the N-terminal half of ECL1 make hydrophobic contacts with a hydrophobic core formed by residues L32, F33, W36, Y65, Y84, L85, P86 and W87 on the αA helix, L2 and L5 of the ECD. Additionally, the negatively charged residues E127 and E129 on the stalk and D208 and D209 on the tip of ECL1 tend to form salt bridges with the basic residues R111 and R116 on the L5 of the ECD. The receptor is shown in cartoon representation. The ECD, stalk, ECL1 and TMD are coloured orange, green, magenta and blue, respectively. The residues involved in the interaction are shown as sticks. b–d, Interaction interfaces on the ECD for the stalk/ECL1 in the molecular dynamics simulations (b), glucagon in the GCGR–glucagon complex model7 (c) and mAb1 in the GCGR–NNC0640–mAb1 complex structure (d). The ECDs of the receptor are shown as grey cartoon and surface. The residues involved in the interactions are shown as sticks and coloured orange.
