Myosin is a key molecular motor in eukaryotes from the plant and animal kingdoms. Interactions between myosin motor domains and actin filaments are powered by the turnover of ATP to generate force and motion in both muscle and non-muscle cells. It is well-known that release of the ATP hydrolysis product inorganic phosphate (orthophosphate; Pi) from the myosin active site is coupled with the main force-generating structural change, the power-stroke. However, due to lack of high-resolution structures of intermediate states there is poor understanding of the sequence of structural changes that couple Pi-release to myosin lever arm swing. Moreover, there is a range of apparently conflicting results from biophysical studies at varied Pi-concentration on isolated proteins to muscle cells. This has led to a range of kinetic and mechanokinetic models with varying temporal relationships between Pi-release and force-generation. Additionally, the effects of varied Pi-concentration on some specific contractile phenomena are particularly poorly understood such as the resistance to stretch of active muscle in eccentric contraction. Finally, several recently developed myosin active drugs affect myosin interstate transitions closely associated with Pi-release.

In this Research Topic we wish to address the central role of Pi-release in actomyosin energy transduction in different myosin classes and key roles of varied Pi-concentration in muscle contraction but also in other contractile phenomena. We welcome contributions in the form of original research, review, mini review, hypothesis and theory, perspective, that cover, but are not limited to, the following aspects:

-Experimental structural studies of the Pi-release mechanism in relation to structural changes in the myosin motor domain from myosin attachment to actin until completion of the power-stroke;
-Molecular modelling, covering similar phases of the actomyosin interaction as the experimental studies mentioned in the previous study;
-Experimental studies of myosin motor function (e.g. mechanical, optical or biochemical kinetic studies) using isolated proteins. Studies focusing on mechanokinetic modelling of such phenomena are also welcome. Of particular interest would be these types of studies focusing on eccentric contraction;
-Mechanisms of muscle fatigue;
-Mechanisms of action and contractile effects of drugs affecting Pi-release;
-Pi-release from myosin in diseases.

Topic Editors declare no conflicts of interest in relation to this Research Topic.

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Release of Inorganic Phosphate from the Myosin Active Site in Actomyosin Energy Transduction