Fig. 6: HRD and DFG motif peptides of profile 2 variants are in unfolded regions. | Nature Communications

Fig. 6: HRD and DFG motif peptides of profile 2 variants are in unfolded regions.

From: Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations

Fig. 6: HRD and DFG motif peptides of profile 2 variants are in unfolded regions.The alternative text for this image may have been generated using AI.

a Mass spectra of a triply charged peptide (MH+ = 2209.2312 Da) containing the HRD motif in wild type (left), ΔL747-A750InsP (blue box), and ΔE746-A750 (red box) at the 10 and 600 s labeling time points. The amino acid sequence of the peptide is shown above the crystal structure (bottom left) and colored green in the structure. The fully deuterated (unfolded) and no deuterium labeling (folded) reference mass spectra are shown below the erlotinib-bound mass spectra. The areas below the light blue and red lines respectively in the bimodal mass envelopes correspond to the protein population within this peptide region (and environment) that is folded and unfolded. Note that erlotinib addition suppressed the unfolded peak in ΔE746-A750 at the 600 s time point. b Mass spectra of a doubly charged peptide (MH+ = 1582.8952 Da) containing the DFG motif in wild type (left), ΔL747-A750InsP (blue box), and ΔE746-A750 (red box) at 10 and 600 s labeling time points. The peptide region is colored green in the crystal structure at bottom left. Note the bimodal distribution seen for ΔE746-A750, which is collapsed to the folded population upon erlotinib addition. Experimental parameters are given in Supplementary Table 1, and source HDX-MS data are provided as a Source Data file.

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