Figure 4.

Fab2 stabilizes GIPR in auto-inhibited conformation. (A) Structure superposition of GIPR-GIP complex with GIPR-Fab2 complex. Fab2 is shown in blue surface. GIPR ECD is shown as cyan cartoon with the stalk region colored in red. Superposed GIP peptide is shown as yellow cartoon. (B) The epitope of GIP and Fab2 on the GIPR ECD. The C-terminal stalk of GIPR is removed for comparison with GIPR-GIP structure. GIPR is shown as cyan surface and the GIP is shown as yellow cartoon. The GIP epitope is colored in orange and the Fab2 epitope is outlined in blue. (C) Sequence alignment of the GIPR ECD stalk and GIP peptide presented in a helical wheel. GIPR stalk peptide residues are in red and GIP peptide residues are in black. The three conserved residues are highlighted in cyan shade. (D) Superposition of the GIP peptide to the ECD C-terminal stalk. GIPR ECD with the C-terminal stalk removed is shown as cyan surface. The C-terminal stalk is shown as red cartoon. Superposed GIP is shown as yellow cartoon. The conserved hydrophobic residues are shown as sticks. (E). Comparison of four Class B GPCR-antibody complex structures. GPCR ECD is shown in white surface. The Fabs are shown in cartoon and color in blue (mAb2), cyan (hGIPR-mAb), green (gipg013), and orange (mAb 3F52) respectively. The C-terminal stalk of GIPR ECD is shown in red cartoon.