Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle

Marco Caremani; Luca Fusi; Massimo Reconditi; Gabriella Piazzesi; Theyencheri Narayanan; Malcolm Irving; Vincenzo Lombardi; Marco Linari; Elisabetta Brunello

doi:10.1085/jgp.202313393

Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle

Marco Caremani, Luca Fusi, Massimo Reconditi, Gabriella Piazzesi, Theyencheri Narayanan, Malcolm Irving, Vincenzo Lombardi, Marco Linari, Elisabetta Brunello^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Contraction of skeletal muscle is triggered by an increase in intracellular calcium concentration that relieves the structural block on actin-binding sites in resting muscle, potentially allowing myosin motors to bind and generate force. However, most myosin motors are not available for actin binding because they are stabilized in folded helical tracks on the surface of myosin-containing thick filaments. High-force contraction depends on the release of the folded motors, which can be triggered by stress in the thick filament backbone, but additional mechanisms may link the activation of the thick filaments to that of the thin filaments or to intracellular calcium concentration. Here, we used x-ray diffraction in combination with temperature-jump activation to determine the steady-state calcium dependence of thick filament structure and myosin motor conformation in near-physiological conditions. We found that x-ray signals associated with the perpendicular motors characteristic of isometric force generation had almost the same calcium sensitivity as force, but x-ray signals associated with perturbations in the folded myosin helix had a much higher calcium sensitivity. Moreover, a new population of myosin motors with a longer axial periodicity became prominent at low levels of calcium activation and may represent an intermediate regulatory state of the myosin motors in the physiological pathway of filament activation.

Original language	English
Journal	Journal of General Physiology
Volume	155
Issue number	12
DOIs	https://doi.org/10.1085/jgp.202313393
Publication status	Published - 4 Dec 2023

Keywords

Mammalian skeletal muscle
muscle regulation
muscle X-ray diffraction

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10.1085/jgp.202313393Licence: CC BY

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title = "Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle",

abstract = "Contraction of skeletal muscle is triggered by an increase in intracellular calcium concentration that relieves the structural block on actin-binding sites in resting muscle, potentially allowing myosin motors to bind and generate force. However, most myosin motors are not available for actin binding because they are stabilized in folded helical tracks on the surface of myosin-containing thick filaments. High-force contraction depends on the release of the folded motors, which can be triggered by stress in the thick filament backbone, but additional mechanisms may link the activation of the thick filaments to that of the thin filaments or to intracellular calcium concentration. Here, we used x-ray diffraction in combination with temperature-jump activation to determine the steady-state calcium dependence of thick filament structure and myosin motor conformation in near-physiological conditions. We found that x-ray signals associated with the perpendicular motors characteristic of isometric force generation had almost the same calcium sensitivity as force, but x-ray signals associated with perturbations in the folded myosin helix had a much higher calcium sensitivity. Moreover, a new population of myosin motors with a longer axial periodicity became prominent at low levels of calcium activation and may represent an intermediate regulatory state of the myosin motors in the physiological pathway of filament activation.",

keywords = "Mammalian skeletal muscle, muscle regulation, muscle X-ray diffraction",

author = "Marco Caremani and Luca Fusi and Massimo Reconditi and Gabriella Piazzesi and Theyencheri Narayanan and Malcolm Irving and Vincenzo Lombardi and Marco Linari and Elisabetta Brunello",

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year = "2023",

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doi = "10.1085/jgp.202313393",

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T1 - Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle

AU - Caremani, Marco

AU - Fusi, Luca

AU - Reconditi, Massimo

AU - Piazzesi, Gabriella

AU - Narayanan, Theyencheri

AU - Irving, Malcolm

AU - Lombardi, Vincenzo

AU - Linari, Marco

AU - Brunello, Elisabetta

PY - 2023/12/4

Y1 - 2023/12/4

N2 - Contraction of skeletal muscle is triggered by an increase in intracellular calcium concentration that relieves the structural block on actin-binding sites in resting muscle, potentially allowing myosin motors to bind and generate force. However, most myosin motors are not available for actin binding because they are stabilized in folded helical tracks on the surface of myosin-containing thick filaments. High-force contraction depends on the release of the folded motors, which can be triggered by stress in the thick filament backbone, but additional mechanisms may link the activation of the thick filaments to that of the thin filaments or to intracellular calcium concentration. Here, we used x-ray diffraction in combination with temperature-jump activation to determine the steady-state calcium dependence of thick filament structure and myosin motor conformation in near-physiological conditions. We found that x-ray signals associated with the perpendicular motors characteristic of isometric force generation had almost the same calcium sensitivity as force, but x-ray signals associated with perturbations in the folded myosin helix had a much higher calcium sensitivity. Moreover, a new population of myosin motors with a longer axial periodicity became prominent at low levels of calcium activation and may represent an intermediate regulatory state of the myosin motors in the physiological pathway of filament activation.

AB - Contraction of skeletal muscle is triggered by an increase in intracellular calcium concentration that relieves the structural block on actin-binding sites in resting muscle, potentially allowing myosin motors to bind and generate force. However, most myosin motors are not available for actin binding because they are stabilized in folded helical tracks on the surface of myosin-containing thick filaments. High-force contraction depends on the release of the folded motors, which can be triggered by stress in the thick filament backbone, but additional mechanisms may link the activation of the thick filaments to that of the thin filaments or to intracellular calcium concentration. Here, we used x-ray diffraction in combination with temperature-jump activation to determine the steady-state calcium dependence of thick filament structure and myosin motor conformation in near-physiological conditions. We found that x-ray signals associated with the perpendicular motors characteristic of isometric force generation had almost the same calcium sensitivity as force, but x-ray signals associated with perturbations in the folded myosin helix had a much higher calcium sensitivity. Moreover, a new population of myosin motors with a longer axial periodicity became prominent at low levels of calcium activation and may represent an intermediate regulatory state of the myosin motors in the physiological pathway of filament activation.

KW - Mammalian skeletal muscle

KW - muscle regulation

KW - muscle X-ray diffraction

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DO - 10.1085/jgp.202313393

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JO - Journal of General Physiology

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ER -

Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle

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