Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity
Figure 5
MD conformations of KIT cytoplasmic region in the native protein and its mutants.
(A) Superposed conformations were selected by RMSDs clustering. Ribbon diagrams display the proteins regions or fragments with different colors: JMR (yellow), A-loop (red), N- and C-lobe (cyan and blue), C-helix in the N-lobe (green), G-helix in C-lobe (purple) and KID (gray). The point mutations in positions 816 and 560 are shown as balls. The earlier reported KITWT and mutant KITD816V are encircled. (B) Superimposed structures of the most representative MD conformations in the native KIT (I) (in wheat), its mutant D816H (II) (in pale cyan) and the crystallographic structure 1T45 (III) (in gray). Ribbon diagrams display the proteins regions or fragments with different colors: (I) JMR in yellow, Cα-helix in green, A-loop in magenta; (II) JMR in orange, Cα-helix in cyan, A-loop in red; (III) JMR in sand, Cα-helix in pale green, A-loop in pink.