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bioRxiv · 10.1101/2023.04.12.535196

New paradigms in actomyosin energy transduction: critical evaluation of non-traditional models for orthophosphate release

Mansson, A.·Usaj, M.·Moretto, L.·Matusovsky, O. S.·Velayuthan, L. P.·Friedmann, R.·Rassier, D. E.
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Abstract

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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Mansson, A., Usaj, M., Moretto, L., Matusovsky, O. S., Velayuthan, L. P., Friedmann, R., Rassier, D. E.. 2023-04-13. New paradigms in actomyosin energy transduction: critical evaluation of non-traditional models for orthophosphate release. https://doi.org/10.1101/2023.04.12.535196

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