Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity
Figure 9
Principal Component Analysis of KIT cytoplasmic region in the inactive state.
Calculation was performed on the backbone atoms of KITWT and mutants, KITD816H/Y/N and KITV560G/D, combining the MD trajectories 1 and 2 (total of 96-ns production simulation time for KITD816H/Y/N mutants, and 130-ns for KITV560G/D mutants) and taking the average MD conformations as references for the RMS fits. (a) A diagram gives the eigenvalues spectra of KITWT (black) and mutants, KITD816V (red), KITD816H (green), KITD816Y (purple), KITD816N (blue), KITV560G (orange) and KITV560D (mauve), in descending order. Atomic components in modes 1–3 for KITWT (b) and modes 1–2 for KIT mutants (c) are drawn as dark grey arrows on the protein cartoon representation. Some regions or fragments of the proteins are displayed with different colors: JMR (yellow), A-loop (red), N- and C-lobe (cyan and blue), the C-helix in the N-terminal (green), the C-terminal helix (purple) and KID (gray).