The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle

Muscle contraction is powered by actin-myosin interaction controlled by Ca2+ via the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical strand that runs along the whole ∼1 μm length of a thin...

Full description

Saved in:
Bibliographic Details
Main Authors: Bershitsky, Sergey Y., Koubassova, Natalia A., Kopylova, Galina V., Ferenczi, Michael Alan, Narayanan, Theyencheri, Tsaturyan, Andrey K.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2017
Subjects:
Online Access:https://hdl.handle.net/10356/82599
http://hdl.handle.net/10220/42317
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-82599
record_format dspace
spelling sg-ntu-dr.10356-825992020-11-01T05:21:55Z The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle Bershitsky, Sergey Y. Koubassova, Natalia A. Kopylova, Galina V. Ferenczi, Michael Alan Narayanan, Theyencheri Tsaturyan, Andrey K. Lee Kong Chian School of Medicine (LKCMedicine) Muscle contraction Regulation Muscle contraction is powered by actin-myosin interaction controlled by Ca2+ via the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical strand that runs along the whole ∼1 μm length of a thin filament. In the absence of Ca2+, Tn that is tightly bound to Tpm binds actin and holds the Tpm strand in the blocked, or B, state, where Tpm shields actin from the binding of myosin heads. Ca2+ binding to Tn releases the Tpm from actin so that it moves azimuthally around the filament axis to a closed, or C, state, where actin is partially available for weak binding of myosin heads. Upon transition of the weak actin-myosin bond into a strong, stereo-specific complex, the myosin heads push Tpm strand to the open, or O, state allowing myosin binding sites on several neighboring actin monomers to become open for myosin binding. We used low-angle x-ray diffraction at the European Synchrotron Radiation Facility to check whether the O- to C-state transition in fully activated fibers of fast skeletal muscle of the rabbit occurs during transition from isometric contraction to shortening under low load. No decrease in the intensity of the second actin layer line at reciprocal radii in the range of 0.15–0.275 nm−1 was observed during shortening suggesting that an azimuthal Tpm movement from the O- to C-state does not occur, although during shortening muscle stiffness is reduced compared to the isometric state, and the intensities of other actin layer lines demonstrate a ∼2-fold decrease in the fraction of myosin heads strongly bound to actin. The data show that a small fraction of actin-bound myosin heads is sufficient for supporting the O-state and, therefore the C-state is not occupied in fully activated skeletal muscle that produces mechanical work at low load. Accepted version 2017-05-03T07:04:03Z 2019-12-06T14:58:44Z 2017-05-03T07:04:03Z 2019-12-06T14:58:44Z 2017 Journal Article Bershitsky, S. Y., Koubassova, N. A., Ferenczi, M. A., Kopylova, G. V., Narayanan, T., & Tsaturyan, A. K. (2017). The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle. Biophysical Journal, 112(7), 1455-1461. 0006-3495 https://hdl.handle.net/10356/82599 http://hdl.handle.net/10220/42317 10.1016/j.bpj.2017.02.017 en Biophysical Journal © 2017 Biophysical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Biophysical Journal, Biophysical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bpj.2017.02.017]. 14 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Muscle contraction
Regulation
spellingShingle Muscle contraction
Regulation
Bershitsky, Sergey Y.
Koubassova, Natalia A.
Kopylova, Galina V.
Ferenczi, Michael Alan
Narayanan, Theyencheri
Tsaturyan, Andrey K.
The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle
description Muscle contraction is powered by actin-myosin interaction controlled by Ca2+ via the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical strand that runs along the whole ∼1 μm length of a thin filament. In the absence of Ca2+, Tn that is tightly bound to Tpm binds actin and holds the Tpm strand in the blocked, or B, state, where Tpm shields actin from the binding of myosin heads. Ca2+ binding to Tn releases the Tpm from actin so that it moves azimuthally around the filament axis to a closed, or C, state, where actin is partially available for weak binding of myosin heads. Upon transition of the weak actin-myosin bond into a strong, stereo-specific complex, the myosin heads push Tpm strand to the open, or O, state allowing myosin binding sites on several neighboring actin monomers to become open for myosin binding. We used low-angle x-ray diffraction at the European Synchrotron Radiation Facility to check whether the O- to C-state transition in fully activated fibers of fast skeletal muscle of the rabbit occurs during transition from isometric contraction to shortening under low load. No decrease in the intensity of the second actin layer line at reciprocal radii in the range of 0.15–0.275 nm−1 was observed during shortening suggesting that an azimuthal Tpm movement from the O- to C-state does not occur, although during shortening muscle stiffness is reduced compared to the isometric state, and the intensities of other actin layer lines demonstrate a ∼2-fold decrease in the fraction of myosin heads strongly bound to actin. The data show that a small fraction of actin-bound myosin heads is sufficient for supporting the O-state and, therefore the C-state is not occupied in fully activated skeletal muscle that produces mechanical work at low load.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Bershitsky, Sergey Y.
Koubassova, Natalia A.
Kopylova, Galina V.
Ferenczi, Michael Alan
Narayanan, Theyencheri
Tsaturyan, Andrey K.
format Article
author Bershitsky, Sergey Y.
Koubassova, Natalia A.
Kopylova, Galina V.
Ferenczi, Michael Alan
Narayanan, Theyencheri
Tsaturyan, Andrey K.
author_sort Bershitsky, Sergey Y.
title The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle
title_short The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle
title_full The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle
title_fullStr The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle
title_full_unstemmed The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle
title_sort closed state of the thin filament is not occupied in fully activated skeletal muscle
publishDate 2017
url https://hdl.handle.net/10356/82599
http://hdl.handle.net/10220/42317
_version_ 1683493849992790016