Hotspot Mutations in KIT Receptor Differentially Modulate Its Allosterically Coupled Conformational Dynamics: Impact on Activation and Drug Sensitivity
Figure 13
Communication pathways of cytoplasmic region in KITWT and KITD816N/Y/H/V mutants.
2D and 3D graphs were drawn with Gephi and PyMOL modules incorporated in MONETA. Left panel: 2D graphs of a global topology illustrating the inter-residues communications in KITWT and KIT mutants. Residues are represented by points, communication pathways (CPs) are depicted by bold lines and two connected residues (by at least on eCP) by a thin line. Residues are coloured from blue through green and yellow to red according to their communication efficiency. The colours are normalized according to the global range of these values for all studied proteins. The C-loop residues are contoured by dotted lines. Middle panel: Large-scale view of the CPs in KIT zoomed on CPs in the JMR and the A-loop. Residues are coloured from blue through green and yellow to red according to their communication efficiency. The colours are normalized according to the range of values for each protein, reflecing a relative communication efficiency of residues in each protein. The C-loop residues are contoured by dotted lines. Each residue is labelled by its number in KIT sequence. Right panel: Average MD conformation presented as cartoon. The residues forming IDSs in the A-loop and the JM-Switch are colored in red and yellow respectively. V559, D792 and Y823 are show in sticks, positions of D816N/Y/H/V are indicated by black points. CPs initiated by either V559 or D792 are represented in bold lines, magenta in KITWT (CPwt only) and black in the mutants.