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A superposition of FXII-FnIE (green) with EGF (pale yellow) bound to EGFR (orange) shows that in the absence of any large conformational changes FXII-FnIE is not able to interact with EGFR because the FnI domain clashes with domain I of EFGR. The conserved arginine in EGF makes a salt bridge with Asp355 of EGFR; the phenylalanine in the EGF-like domain of FXII does not facilitate such an interaction (EGF-EGFR structure; PDB entry 1ivo; Ogiso et al., 2002 ▶).
