Pi Release from Myosin: A Simulation Analysis of Possible Pathways

SummaryThe release of phosphate (Pi) is an important element in actomyosin function and has been shown to be accelerated by the binding of myosin to actin. To provide information about the structural elements important for Pi release, possible escape pathways from various isolated myosin II structures have been determined by molecular dynamics simulations designed for studying such slow processes. The residues forming the pathways were identified and their role was evaluated by mutant simulations. Pi release is slow in the pre-powerstroke structure, an important element in preventing the powerstroke prior to actin binding, and is much more rapid for Pi modeled into the post-rigor and rigor-like structures. The previously proposed backdoor route is dominant in the pre-powerstroke and post-rigor states, whereas a different path is most important in the rigor-like state. This finding suggests a mechanism for the actin-activated acceleration of Pi release.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (560 K)Download as PowerPoint slideHighlights► Pathways for Pi release from myosin II are determined at atomic resolution ► The escape barrier is compared in various myosin II structures ► The origin of the high-release barrier in the myosin pre-powerstroke is described ► A novel mechanism for accelerated Pi release from actomyosin is proposed