Fig. 7: Model for a two-step structural mechanism of MT-stimulated ADP release.

Schematic illustrating a proposed two-step structural mechanism of MT-stimulated ADP release, showing movements of key SSEs and side chains relative to the static helix α2a and P-loop. MT binding triggers transition to an apo-like state, including helix α4 extension and twisting of core β-sheet (β-core) along with movements of overlying helix α3 and loop 9 elements. These movements dismantle a hydrogen bonding network involving D231 and T92 that coordinates Mg²⁺ through a water ‘cap’ (blue dashed lines). This drives Mg²⁺ out of the complex, with D231 forming a new bonding network with R190 and K91 (red dashed lines). These changes disrupt key bonds stabilizing ADP’s β-phosphate (cyan dashed lines), leaving ADP only weakly coordinated by remaining contacts with helix α2a and the P-loop, promoting its subsequent release mediated by loop 9 dynamics. α and β are α-phosphate and β-phosphate, respectively.