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. 2020 Feb 18;15(2):e0229077. doi: 10.1371/journal.pone.0229077

Fig 3. Model.

Fig 3

Upon EGF binding, the ECD (contains domains I-IV) of EGFR switches from a closed, inactive (‘tethered’) state to an open, active (‘untethered’) state. Upon CTX selection (CTX interacts with domain III of tethered EGFR thereby preventing EGF binding), HNSCC cells acquire EGFR mutations (G33S, N56K) in domain I, which leads to ligand-independent activation and prevents receptor internalization/degradation. Mutant EGFR does not bind CTX since it is ‘trapped’ in the open confirmation, leading to CTX resistance.