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Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism

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Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism. / Paul, Danielle; Squire, John; Morris, Edward.

In: Journal of Structural Biology, Vol. 197, No. 3, 03.2017, p. 365-371.

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Paul, Danielle ; Squire, John ; Morris, Edward. / Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism. In: Journal of Structural Biology. 2017 ; Vol. 197, No. 3. pp. 365-371.

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@article{4166529c4364462883417f192dab585d,
title = "Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism",
abstract = "The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca2+ using electron microscopy and reference-free single particle analysis. The resulting density maps have been fitted with atomic models of actin, tropomyosin and troponin showing that: (i) the polarity of the troponin complex is consistent with our 2009 findings, with large shape changes in troponin between the two states; (ii) without Ca2+ the tropomyosin pseudo-repeats all lie at almost equivalent positions in the ‘blocked’ position on actin (over subdomains 1 and 2); (iii) in the active state the tropomyosin pseudo-repeats are all displaced towards subdomains 3 and 4 of actin, but the extent of displacement varies within the regulatory unit depending upon the axial location of the pseudo-repeats with respect to troponin. Individual pseudo-repeats with Ca2+ bound to troponin can be assigned either to the ‘closed’ state, a partly activated conformation, or the ‘M-state’, a fully activated conformation which has previously been thought to occur only when myosin heads bind. These results lead to a modified view of the steric blocking model of thin filament regulation in which cooperative activation is governed by troponin-mediated local interactions of the pseudo-repeats of tropomyosin with actin.",
keywords = "Actin, Tropomyosin, Troponin, Thin filament, Regulation",
author = "Danielle Paul and John Squire and Edward Morris",
year = "2017",
month = "3",
doi = "10.1016/j.jsb.2017.01.004",
language = "English",
volume = "197",
pages = "365--371",
journal = "Journal of Structural Biology",
issn = "1047-8477",
publisher = "Academic Press",
number = "3",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism

AU - Paul, Danielle

AU - Squire, John

AU - Morris, Edward

PY - 2017/3

Y1 - 2017/3

N2 - The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca2+ using electron microscopy and reference-free single particle analysis. The resulting density maps have been fitted with atomic models of actin, tropomyosin and troponin showing that: (i) the polarity of the troponin complex is consistent with our 2009 findings, with large shape changes in troponin between the two states; (ii) without Ca2+ the tropomyosin pseudo-repeats all lie at almost equivalent positions in the ‘blocked’ position on actin (over subdomains 1 and 2); (iii) in the active state the tropomyosin pseudo-repeats are all displaced towards subdomains 3 and 4 of actin, but the extent of displacement varies within the regulatory unit depending upon the axial location of the pseudo-repeats with respect to troponin. Individual pseudo-repeats with Ca2+ bound to troponin can be assigned either to the ‘closed’ state, a partly activated conformation, or the ‘M-state’, a fully activated conformation which has previously been thought to occur only when myosin heads bind. These results lead to a modified view of the steric blocking model of thin filament regulation in which cooperative activation is governed by troponin-mediated local interactions of the pseudo-repeats of tropomyosin with actin.

AB - The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca2+ using electron microscopy and reference-free single particle analysis. The resulting density maps have been fitted with atomic models of actin, tropomyosin and troponin showing that: (i) the polarity of the troponin complex is consistent with our 2009 findings, with large shape changes in troponin between the two states; (ii) without Ca2+ the tropomyosin pseudo-repeats all lie at almost equivalent positions in the ‘blocked’ position on actin (over subdomains 1 and 2); (iii) in the active state the tropomyosin pseudo-repeats are all displaced towards subdomains 3 and 4 of actin, but the extent of displacement varies within the regulatory unit depending upon the axial location of the pseudo-repeats with respect to troponin. Individual pseudo-repeats with Ca2+ bound to troponin can be assigned either to the ‘closed’ state, a partly activated conformation, or the ‘M-state’, a fully activated conformation which has previously been thought to occur only when myosin heads bind. These results lead to a modified view of the steric blocking model of thin filament regulation in which cooperative activation is governed by troponin-mediated local interactions of the pseudo-repeats of tropomyosin with actin.

KW - Actin

KW - Tropomyosin

KW - Troponin

KW - Thin filament

KW - Regulation

U2 - 10.1016/j.jsb.2017.01.004

DO - 10.1016/j.jsb.2017.01.004

M3 - Article

C2 - 28161413

VL - 197

SP - 365

EP - 371

JO - Journal of Structural Biology

JF - Journal of Structural Biology

SN - 1047-8477

IS - 3

ER -