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Figure 4.
Location of the mAb806/175 epitope in EGFR. (A) Cα trace of
the ectodomain for untethered EGFR1–621. L1 is at the top with
L1 and L2 in teal, CR1 and CR2 in blue, and TGF-α in olive. The
mAb806/175 epitope is drawn in red, with the preceding loop
(residues 271–286) in orange and the disulfide bonds in
yellow. The model was constructed by docking the EGFR-ECD CR2
domain from the tethered conformation (36) onto the structure of
an untethered EGFR monomer in the presence of its ligand (24).
(B) Untethered EGFR ectodomain (as in A) showing the spacial
overlap with the mAb175 Fab (solvent contact surface with the
light chain in yellow and the heavy chain in green). The Fab was
positioned by superimposing the EGFR[287–302] peptide on the
corresponding region of EGFR. The CR1 domain is almost
completely buried within the Fab. (C) Detail of A, viewed from
the right, showing how the preceding disulfide-bonded loop
blocks access to the epitope.
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