Key result
Alternative phosphate-release models redefine the kinetics linking orthophosphate release to the myosin power-stroke.
Why the study?
The relative timing between Pi-release and the myosin power-stroke remains poorly understood, hampering in-depth understanding of force and motion production in health and disease and the mechanism of myosin-active drugs.
Provides a critical evaluation of non-traditional models for orthophosphate release in myosin, guiding future biophysical studies on muscle contraction.
Answers are grounded in this paper and cite their sources.
Challenges single-step Pi-release dogma in myosin; leaves open empirical validation of multistep or branched models for power-stroke timing.
Release of the ATP hydrolysis product inorganic phosphate (Pi) from the active site of myosin is central in chemo-mechanical energy transduction and closely associated with the main force-generating structural change, the power-stroke. Despite intense investigations, the relative timing between Pi-release and the power-stroke remains poorly understood. This hampers in depth understanding of the production of force and motion by myosin in health and disease and also our understanding of myosin-active drugs. From the 1990s and up to today, models with the Pi-release either distinctly before or after the power-stroke, in unbranched kinetic schemes, have dominated the literature. However, in recent years, alternative models have emerged to explain apparently contradictory findings. Here, we first compare and critically analyze, three influential alternative models, either characterized by a branched kinetic scheme or by partial uncoupling of Pi-release and the power-stroke. Finally, we suggest critical tests of the models aiming for a unified picture.
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Månsson et al. (2023) conducted a review in Actomyosin energy transduction. Alternative models for orthophosphate release vs. Conventional models was evaluated. Alternative models for orthophosphate release, including multistep, loose coupling, and branched models, offer new paradigms to explain the temporal relationship between Pi-release and the myosin power-stroke.
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