Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2
Familial Hypertrophic cardiomyopathy (HCM) causes ventricle walls to thicken and often leads to sudden death especially in adults. Mutations in the subfragment 2 (S2) of β-cardiac myosin are implicated in the genetic disorder. This S2 region is a coiled-coil rod region resulting from the di...
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ndltd-unt.edu-info-ark-67531-metadc284142017-03-17T08:39:25Z Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 Dunn, James W. Motor proteins piconewton gravity force spectra Myosin. Heart -- Hypertrophy. Mutation (Biology) Familial Hypertrophic cardiomyopathy (HCM) causes ventricle walls to thicken and often leads to sudden death especially in adults. Mutations in the subfragment 2 (S2) of β-cardiac myosin are implicated in the genetic disorder. This S2 region is a coiled-coil rod region resulting from the dimeric form of myosin II. It has been proposed that an elastic quality allows normal S2 to absorb force during the powerstroke according to the sliding filament model. To test the flexibility of single molecules of S2 against levels of physiological force, the Gravitational Force Spectrometer (GFS) is being developed. This novel system employs a standard microscope on an equatorial mount that allows the spectrometer to be rotated freely in space. Stationary glass beads are attached to a microscope slide where the molecule is tethered between the stationary bead and a smaller mobile bead. The GFS is oriented so that the force of gravity can act on the mobile bead and so impart a small force to the tethered subfragment. Additionally, a video system in conjunction with ImageJ software makes a distance measurement of the molecule possible with a resolution of around 11 nm. The S2 can be stretched parallel or perpendicular to the coiled coil to elucidate different structural properties of the rod. This study is the first to show structural evidence that S2 in vertebrate skeletal myosin uncoils proportionally to physiological force loads. Because of this, the usefulness and promise of the novel GFS is highlighted, and the biological role of S2's flexibility can be directly commented on. If the dimer undergoes uncoiling at physiological force loads as shown, then it is reasonable to think that this might occur in nature in response to the stress of the powerstroke on a single molecule. This unwinding could be to absorb force as a mechanism to protect the muscle fiber. University of North Texas Root, Douglas D. Benjamin, Robert C. O'Donovan, Gerard 2010-05 Thesis or Dissertation Text oclc: 667596669 untcat: b3866917 https://digital.library.unt.edu/ark:/67531/metadc28414/ ark: ark:/67531/metadc28414 English Public Copyright Dunn, James W. Copyright is held by the author, unless otherwise noted. All rights reserved. |
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English |
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Motor proteins piconewton gravity force spectra Myosin. Heart -- Hypertrophy. Mutation (Biology) |
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Motor proteins piconewton gravity force spectra Myosin. Heart -- Hypertrophy. Mutation (Biology) Dunn, James W. Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 |
description |
Familial Hypertrophic cardiomyopathy (HCM) causes ventricle walls to thicken and often leads to sudden death especially in adults. Mutations in the subfragment 2 (S2) of β-cardiac myosin are implicated in the genetic disorder. This S2 region is a coiled-coil rod region resulting from the dimeric form of myosin II. It has been proposed that an elastic quality allows normal S2 to absorb force during the powerstroke according to the sliding filament model. To test the flexibility of single molecules of S2 against levels of physiological force, the Gravitational Force Spectrometer (GFS) is being developed. This novel system employs a standard microscope on an equatorial mount that allows the spectrometer to be rotated freely in space. Stationary glass beads are attached to a microscope slide where the molecule is tethered between the stationary bead and a smaller mobile bead. The GFS is oriented so that the force of gravity can act on the mobile bead and so impart a small force to the tethered subfragment. Additionally, a video system in conjunction with ImageJ software makes a distance measurement of the molecule possible with a resolution of around 11 nm. The S2 can be stretched parallel or perpendicular to the coiled coil to elucidate different structural properties of the rod. This study is the first to show structural evidence that S2 in vertebrate skeletal myosin uncoils proportionally to physiological force loads. Because of this, the usefulness and promise of the novel GFS is highlighted, and the biological role of S2's flexibility can be directly commented on. If the dimer undergoes uncoiling at physiological force loads as shown, then it is reasonable to think that this might occur in nature in response to the stress of the powerstroke on a single molecule. This unwinding could be to absorb force as a mechanism to protect the muscle fiber. |
author2 |
Root, Douglas D. |
author_facet |
Root, Douglas D. Dunn, James W. |
author |
Dunn, James W. |
author_sort |
Dunn, James W. |
title |
Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 |
title_short |
Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 |
title_full |
Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 |
title_fullStr |
Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 |
title_full_unstemmed |
Stretching the Flexible Myosin II Subfragment Using the Novel Gravitational Force Spectroscope, and the Uncoiling of S2 |
title_sort |
stretching the flexible myosin ii subfragment using the novel gravitational force spectroscope, and the uncoiling of s2 |
publisher |
University of North Texas |
publishDate |
2010 |
url |
https://digital.library.unt.edu/ark:/67531/metadc28414/ |
work_keys_str_mv |
AT dunnjamesw stretchingtheflexiblemyosiniisubfragmentusingthenovelgravitationalforcespectroscopeandtheuncoilingofs2 |
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1718430055990820864 |