Figure 2

A global survey of HDX-MS profiles of eIGF1R in response to IGF-1 and VHH-IR5 binding. (a) IGF-1 response profile projected on a structural model of the 1:1 eIGF1R:IGF-1 complex (PDB: 6PYH). The (αβ) ′ monomer, except for α-CT′, is rendered as a transparent surface, while the (αβ) monomer and α-CT′ are shown as a ribbon cartoon. The schematic in the inset shows the domain organization of IGF1R where the (αβ) monomer is colored in green, and (αβ)′ in black. (b) VHH-IR5 response profile projected on the same structural model as in (a) (PDB: 6PYH), except that the structure is rotated counterclockwise by 90°. Significant structural destabilizations are shown in red, stabilizations in blue, lack of significant changes in grey, and missing sequence coverage in black. Residues are colored based on differences in deuteration at a single time point (± 2 SD, p = 0.02). In both (a) and (b), IGF-1 molecules are shown as magenta spheres. Of note, residues of the rhesus eIGF1R used for HDX-MS data collection were mapped by BLAST onto the mouse eIGF1R before rendering the HDX-MS results onto the 3D structure of mouse eIGF1R (PDB: 6PYH).