Figure 3
From: Anti-EGFR antibody 528 binds to domain III of EGFR at a site shifted from the cetuximab epitope
(A) Superposed anti-sEGFR antibody structure. Crystal structures of cetuximab (PDBID 1YY9, orange), panitumumab (PDBID 5SX4, blue), and necitumumab (PDBID 6B3S, magenta) antibodies complexed with domain III of sEGFR (light purple). Possible positioning of 528 Fab deduced from the electron micrograph images is indicated with a green dashed line. A black arrow indicates the viewpoint direction for (B). A loop comprising residues 353–362 is shown in cyan. (B) Manual docking model between domain III (light purple) and 528 (green). CDR loops are colored in blue and the 353–362 loop of sEGFR is in cyan. (C) Mutational residues of domain III induced by the cetuximab treatment (labeled with black characters). The possible binding site of 528 is indicated with a green dashed circle. Panitumumab epitope is colored with purple. The panitumumab epitope overlapping with the cetuximab-induced mutation is colored with yellow. Ser 492 is shown in blue.
