Figure 6. Correlation between Abl kinase activity, imatinib-induced Abl core disassembly, and αI-helix mutations.

(A) Correlation between the PC1 scores of the SH3SH2 resonances (PCA in Figure 3B) of all imatinib complexes and the respective kinase activity (Figure 5B). (B) Correlation between the PC2 scores of the SH3SH2KD resonances of all apo forms (PCA in Figure 4D) and the respective kinase activity (Figure 5B). The color code for the Abl constructs follows panel A. (C) Correlation between the PC1 scores of the SH3SH2 resonances of all imatinib complexes (Figure 3B) and the PC2 scores of the SH3SH2KD resonances of all apo forms (Figure 4D). The color code for the Abl constructs follows panel A. (D) Residues with absolute PC1 loadings larger than 0.15 from the PCA of the SH3SH2 resonances of all imatinib complexes (Figure 3C) indicated as red spheres within the structure of the assembled Abl core (PDB 2FO0). (E) Residues with absolute PC2 loadings larger than 0.1 from the PCA of the SH3SH2KD resonances of all apo forms (Figure 4D, Figure 4—figure supplement 1) indicated as red spheres within the structure of the assembled Abl core. (F) Interface between the αI-helix and the SH2 domain. The bent αI-helix of the assembled core structure is shown in cyan. The straight αI-helix of the isolated Abl kinase domain (PDB 1M52) is shown in magenta stick representation, while residues that clash with the SH2 domain of the assembled Abl core being shown in green stick representation. SH2 residues are displayed as colored spheres. Red: residues with absolute PC2 loadings >0.1 as in panel E, blue: residues with absolute PC2 loadings smaller than 0.1, yellow: residues with unresolved resonances in NMR spectrum.