The combined association of Ca(II) and rigor myosin heads with the thin filament accelerates the rate of inorganic phosphate dissociation approximately 100-fold during the actomyosin cycle.
The principal influence of the thin filament in striated muscle contraction is setting the rate of Pi dissociation, dependent on the liganded state and myosin conformation.
Striated muscle contraction occurs when myosin undergoes a lever-type structural change. This process (the power stroke) requires ATP and is governed by the thin filament, a complex of actin, tropomyosin, and troponin. The authors have used a fast-mixing instrument to investigate the mechanism of regulation. Such (pre-steady-state kinetic) experiments allow biochemical intermediates in a working actomyosin cycle to be monitored. The regulatory focal point is demonstrated to be the step that involves the departure of inorganic phosphate (i.e., AM-ADP-Pi → AM-ADP). This part of the cycle, which lies on the main kinetic pathway and coincides with the drive stroke, is maximally accelerated ∼100-fold by the combined association of ligands (CaII and rigor myosin heads) with the thin filament. However, the observed ligand dependencies of the rates of Pi dissociation that are reported herein are at variance with predictions of models derived from experiments where ATP hydrolysis is not taking place (and myosin exists in a nonphysiological form). It is concluded that the principal influence of the thin filament is in setting the rate of Pi dissociation and that physiological levels of regulation are dependent upon the liganded state of the thin filament as well as the conformation of myosin.
Heeley et al. (2019) studied Striated muscle contraction. Ligand association (Ca[II] and rigor myosin heads) was evaluated on Rate of inorganic phosphate (Pi) dissociation. The combined association of Ca(II) and rigor myosin heads with the thin filament accelerates the rate of inorganic phosphate dissociation approximately 100-fold during the actomyosin cycle.