Fig. 3: Crystal structure of Fab ch128.1/IgG1 and docking model of Fab binding to hTfR1.

a Structure of the Fab ch128.1/IgG1 highlighting the CDRs. On the left is a schematic representation of the antibody Fab fragment showing in light blue the light chain, in orange the position of the light chain CDRs (L1, L2, and L3), in blue the heavy chain and in green the heavy chain CDRs (H1, H2, and H3). On the right is a 3D surface representation of the Fab. The images were generated with PyMOL. b Computational modeling of Fab ch128.1/IgG1 binding to hTfR1. PyRosetta binding funnel generated from the largest cluster of docking models obtained with ClusPro. Each dot shows the PyRosetta binding score in Rosetta energy units (REU) and the RMSD from the initial configuration for the 17,003 docking models generated. c Surface representation of the MACV GP1 in complex with the hTfR1 crystal structure (PDB ID:3KAS) and of the Fab ch128.1/IgG1-hTfR1 docking model. Shown on top is the surface representation of MACV GP1 (pink) in complex with the hTfR1 with the helical (H, yellow), protease-like (P, green) and apical (A, white) domains in front view, rotated 90° on the y axis (lateral) and rotated 90° on the x axis (top). Below is the Fab ch128.1/IgG1-hTfR1 docking model with the same views with the heavy chain in blue and the light chain in light blue. It is important to note the steric overlap between the structures of the Fab ch128.1/IgG1 docking model and the MACV GP1 bound to the apical domain of hTfR1. Note that the Fab ch128.1/IgG1 CDRs are not represented by different colors in this panel. d Overlap of the MACV GP1 and the predicted Fab ch128.1/IgG1 footprints on hTfR1. Surface representation of hTfR1 with the front, lateral, and top orientations as in panel (c), showing on the apical domain the footprint of the MACV GP1 in pink and the footprint of the predicted Fab ch128.1/IgG1 docking model colored in blue for the heavy chain and light blue for the light chain. The overlapping contacts are shown in red.