Abstract
The molecular motor myosin V transports cargo by stepping on actin filaments, executing a random diffusive search for actin binding sites at each step. A recent experiment suggests that the joint between the myosin lever arms may not rotate freely, as assumed in earlier studies, but instead has a preferred angle giving rise to structurally constrained diffusion. We address this controversy through comprehensive analytical and numerical modeling of myosin V diffusion and stepping. When the joint is constrained, our model reproduces the experimentally observed diffusion, allowing us to estimate bounds on the constraint energy. We also test the consistency between the constrained diffusion model and previous measurements of step size distributions and the load dependence of various observable quantities. The theory lets us address the biological significance of the constrained joint and provides testable predictions of new myosin behaviors, including the stomp distribution and the run length under off-axis force.
Highlights
Molecular motors are cellular machines that function by converting chemical energy into mechanical work (Schliwa and Woehlke, 2003)
We describe the main features of our polymer structural model for myosin V, the actin filament geometry, and how the model allows us to predict diffusion and stepping behavior, including the probabilities of various kinetic pathways
Following Hinczewski et al (2013), we model the actin-binding heads and lever arm domains of myosin V as semi-flexible polymer chains with length L and persistence length lp
Summary
Molecular motors are cellular machines that function by converting chemical energy into mechanical work (Schliwa and Woehlke, 2003). The motor walks forward along the actin, stepping hand-over-hand, by alternating head detachment, with the free head performing a diffusive search for actin binding sites during each step (Shiroguchi and Kinosita, 2007). Such unidirectional motility requires coordination between the two heads with preferential detachment of the rear head, the so called ‘gating’ mechanism, which is regulated by the strain within the lever arms while the heads are bound to actin (Veigel et al, 2002; Veigel et al, 2005; Purcell et al, 2005; Sakamoto et al, 2008).
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