Direct visualization of single molecules revealed that two myosin heads are required to activate a thin filament regulatory unit, which can subsequently accommodate 11 additional myosins.
Direct single-molecule imaging demonstrates that two myosin heads are required to activate a thin filament regulatory unit, enabling cooperative binding of up to 11 additional myosins.
Contraction of striated muscle is tightly regulated by the release and sequestration of calcium within myocytes. At the molecular level, calcium modulates myosin's access to the thin filament. Once bound, myosin is hypothesized to potentiate the binding of further myosins. Here, we directly image single molecules of myosin binding to and activating thin filaments. Using this approach, the cooperative binding of myosin along thin filaments has been quantified. We have found that two myosin heads are required to laterally activate a regulatory unit of thin filament. The regulatory unit is found to be capable of accommodating 11 additional myosins. Three thin filament activation states possessing differential myosin binding capacities are also visible. To describe this system, we have formulated a simple chemical kinetic model of cooperative activation that holds across a wide range of solution conditions. The stochastic nature of activation is strongly highlighted by data obtained in sub-optimal activation conditions where the generation of activation waves and their catastrophic collapse can be observed. This suggests that the thin filament has the potential to be turned fully on or off in a binary fashion.
Desai et al. (Thu,) conducted a other in Muscle contraction mechanism (in vitro). Fluorescent Myosin S1 was evaluated on Number of myosin heads required to activate a thin filament. Direct visualization of single molecules revealed that two myosin heads are required to activate a thin filament regulatory unit, which can subsequently accommodate 11 additional myosins.