Myosin V executes steps of variable length via structurally constrained diffusion

Abstract
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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.

Data availability

All the data for the figures in the study (Fig. 3-8), along with the corresponding code to process the data and produce the figures, is included in the source data file uploaded with the submission.

Article and author information

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David Hathcock

Department of Physics, Cornell University, Ithaca, United States

For correspondence
dch242@cornell.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4551-9239
Riina Tehver

Department of Physics and Astronomy, Denison University, Granville, United States

Competing interests
The authors declare that no competing interests exist.
Michael Hinczewski

Department of Physics, Case Western Reserve University, Cleveland, United States

For correspondence
mxh605@case.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2837-7697
Dave Thirumalai

Department of Chemistry, University of Texas, Austin, Austin, United States

Competing interests
The authors declare that no competing interests exist.

Funding

National Science Foundation (DGE-1650441)

David Hathcock

National Science Foundation (CHE 19-00033)

Dave Thirumalai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.