FIGURE 3.

HDX-MS heat maps for EGFR, HER2, and HER3 ICH constructs. Residue-specific average deuterium uptake data, 〈%n_ex〉, is mapped against respective EGFR, HER2, and HER3 sequences. Deuterium uptake reaches a plateau much sooner in C-terminal tail regions when compared with the more structured kinase domain. The EGFR sequence includes the 24-residue signal peptide in the numbering scheme. Similarly, the HER3 sequence numbering includes the 19-residue signal peptide. The secondary structure of the kinase domain as determined by X-ray crystallography is shown plotted against the sequence (Protein Data Bank codes 3PP0 for HER2, 3KEX for HER3, and 2GS2 for EGFR) (63–65). The location of αC-helices and activation loops are also identified.