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.
- David Hathcock
- Dave Thirumalai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Taekjip Ha, Johns Hopkins University, United States
- Received: September 3, 2019
- Accepted: January 14, 2020
- Accepted Manuscript published: January 15, 2020 (version 1)
© 2020, Hathcock et al.
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