Fig. 4: A mechanokinetic model incorporating a secondary Pi-binding site outside the active site.
From: Multistep orthophosphate release tunes actomyosin energy transduction
a A kinetic scheme with Pi-binding outside the active site, as indicated by circles in the second row. The Pi-dissociation rate constant (kP+) from the AMDP´L, AMDP´H and AM/AMDP´ states (blue, red and orange in the middle row) to the AMDL, AMDH and AM/AMD states and the reverse second order association rate constant kP−´ are related as KC = kP+/kP−´. Thus, a pseudo-first-order Pi-association rate constant, kP− = kP+[Pi]/KC applies for a given Pi-concentration. Short notations for states, as also used in Fig. 4b and elsewhere, are indicated in boxes. b The free energy vs the cross-bridge strain variable x for critical states of the model at 0.5 mM Pi. The Pi in the AMDP´L, the AMDP´H, and the (AM/AMD)P´ states is assumed to be bound to sites outside the active site. The Pi in these states is released at a similar rate (kp+) from each of the states. Black straight lines refer to detached cross-bridge states. c Simulated steady-state values for the maximum isometric force (black circles) and maximum velocity of shortening (black squares) compared to experimental data (purple) for the velocity11,104 (10 °C) and force5 at 30 and 5 °C. The steady-state isometric force for the simplified model in Supplementary Fig. 8 is also shown (gray stars). d Simulation of power strokes (nm displacement vs time) for an ensemble of myosin heads attaching in AMDPPP state and cross-bridge force clamped to 0 pN. For further details of the model, see Methods and Supplementary Tables 5–7.
