Fig. 4: IM459N21 solution structure and comparison of the modes of binding of IM172N22 and insulin.
From: Activation of the human insulin receptor by non-insulin-related peptides
a Correspondence of the backbone conformation of the hIR-bound IM172N22 peptide (green) with that of IM459N21 peptide (grey) determined in solution (for clarity, only six of the NMR-based IM459N21 models are shown). The orange bonds depict the IM172N22 cysteine residues and their associated disulfide bond; the white bonds depict those of IM459N21. Selected IM172N22 residues are labelled. b Overlay of the structure of IM172N22 (green) bound to domain FnIII-1′ (grey) with that of insulin (A chain pink, B chain dark blue) bound to the same domain (PDB 6SOF)5. The orange bonds depict the disulfide linkages within IM172N22 and within insulin. c, Correspondence of key [FnIII-1′]-engaging residues of IM172N22 with those of insulin. Chain termini are labelled and colors are as in panel b. d Proximity (asterisked) of the N terminus of a Site 1 peptide with that of the C terminus of a Site 2 peptide within the map of the IM459-bound hIR ectodomain. Peptides models are derived respectively from PDB 5J3H (S519C16 bound to the hIR L1-CR module12) and from the IM172N22-bound IRΔβ-zip structure presented in this manuscript. The IM172N22 peptide is in green, the S519C16 peptide is in light magenta, receptor domain colors are as in the primary structure domain layout provided in Supplementary Fig. 2a.
