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Myosin V executes steps of variable length via structurally constrained diffusion

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 pr...

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Autores principales: Hathcock, David, Tehver, Riina, Hinczewski, Michael, Thirumalai, D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054003/
https://www.ncbi.nlm.nih.gov/pubmed/31939739
http://dx.doi.org/10.7554/eLife.51569
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author Hathcock, David
Tehver, Riina
Hinczewski, Michael
Thirumalai, D
author_facet Hathcock, David
Tehver, Riina
Hinczewski, Michael
Thirumalai, D
author_sort Hathcock, David
collection PubMed
description 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.
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spelling pubmed-70540032020-03-05 Myosin V executes steps of variable length via structurally constrained diffusion Hathcock, David Tehver, Riina Hinczewski, Michael Thirumalai, D eLife Physics of Living Systems 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. eLife Sciences Publications, Ltd 2020-01-15 /pmc/articles/PMC7054003/ /pubmed/31939739 http://dx.doi.org/10.7554/eLife.51569 Text en © 2020, Hathcock et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Physics of Living Systems
Hathcock, David
Tehver, Riina
Hinczewski, Michael
Thirumalai, D
Myosin V executes steps of variable length via structurally constrained diffusion
title Myosin V executes steps of variable length via structurally constrained diffusion
title_full Myosin V executes steps of variable length via structurally constrained diffusion
title_fullStr Myosin V executes steps of variable length via structurally constrained diffusion
title_full_unstemmed Myosin V executes steps of variable length via structurally constrained diffusion
title_short Myosin V executes steps of variable length via structurally constrained diffusion
title_sort myosin v executes steps of variable length via structurally constrained diffusion
topic Physics of Living Systems
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054003/
https://www.ncbi.nlm.nih.gov/pubmed/31939739
http://dx.doi.org/10.7554/eLife.51569
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AT tehverriina myosinvexecutesstepsofvariablelengthviastructurallyconstraineddiffusion
AT hinczewskimichael myosinvexecutesstepsofvariablelengthviastructurallyconstraineddiffusion
AT thirumalaid myosinvexecutesstepsofvariablelengthviastructurallyconstraineddiffusion