Myosin V executes steps of variable length via structurally constrained diffusion

  1. David Hathcock  Is a corresponding author
  2. Riina Tehver
  3. Michael Hinczewski  Is a corresponding author
  4. Dave Thirumalai
  1. Cornell University, United States
  2. Denison University, United States
  3. Case Western Reserve University, United States
  4. University of Texas, Austin, United States

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

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4551-9239
  2. Riina Tehver

    Department of Physics and Astronomy, Denison University, Granville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2837-7697
  4. 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.

Reviewing Editor

  1. Taekjip Ha, Johns Hopkins University, United States

Publication history

  1. Received: September 3, 2019
  2. Accepted: January 14, 2020
  3. Accepted Manuscript published: January 15, 2020 (version 1)
  4. Version of Record published: March 3, 2020 (version 2)

Copyright

© 2020, Hathcock et al.

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.

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  1. David Hathcock
  2. Riina Tehver
  3. Michael Hinczewski
  4. Dave Thirumalai
(2020)
Myosin V executes steps of variable length via structurally constrained diffusion
eLife 9:e51569.
https://doi.org/10.7554/eLife.51569

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