Figure 7. Mechanical model of Abl allosteric regulation.
(A) Transition between closed (left) and open (right) conformation of Abl’s regulatory core during activation. Arrows indicate mobility of the KD N-lobe and the αI-helix. Clashes between SH3 and KD-N and between SH2 and αI-helix resulting from this mobility are shown by red dots, the related clash-induced forces FKD-N,SH3 and FαI,SH2 by red triangles. Color coding: SH3 (green), SH2 (yellow), KD (blue), αI-helix (cyan), A-loop (inactive: magenta, active: green), P-loop (orange), tyrosine substrate (brown), R479-E528 salt bridge (orange). (B) Model of imatinib-induced Abl core disassembly. The color code follows panel A. Allo: allosteric inhibitor. (C) Detailed model of the interaction between the αI-helix and the SH2 domain for the various investigated Abl αI-helix constructs and inhibitor-bound conformations. The observed, respective Abl activity increases in the direction of the arrow at the bottom. The color code follows panel A.