Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle.
Dependence of myosin filament structure on intracellular calcium concentration in skeletal muscle.
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DOI：
10.1085/jgp.202313393
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发表时间：
2023-12-04
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影响因子：
--
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骨骼肌中的粗丝结构对钙比等长力更敏感，具有更高的协同性。在部分钙活化下，形成了一种新的粗丝结构，其中肌球蛋白马达具有较长的轴向周期性。骨骼肌的收缩是由细胞内钙浓度的增加引起的，钙浓度的增加缓解了静息肌肉中肌动蛋白结合位点的结构阻滞，可能使肌球蛋白马达结合并产生力。然而，大多数肌凝蛋白马达不能用于肌动蛋白结合，因为它们在含有肌凝蛋白的粗丝表面的折叠螺旋轨道上稳定。高强度收缩依赖于折叠马达的释放，这可以由粗丝主干的应力触发，但其他机制可能将粗丝的激活与细丝的激活或细胞内钙浓度联系起来。在这里，我们使用x射线衍射结合温度跳变激活来确定近生理条件下粗丝结构和肌球蛋白运动构象的稳态钙依赖性。我们发现，与垂直电机特征的等距力产生相关的x射线信号与力具有几乎相同的钙敏感性，但与折叠肌球蛋白螺旋中的扰动相关的x射线信号具有更高的钙敏感性。此外，在低钙激活水平下，具有较长轴向周期的新肌球蛋白运动群体变得突出，这可能代表了肌球蛋白运动在纤维激活生理途径中的中间调节状态。
Thick filament structure in skeletal muscle is more sensitive to calcium than isometric force, with a higher cooperativity. A novel thick filament structure in which myosin motors take up a longer axial periodicity is formed at partial calcium activation. 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.
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DOI：
10.1085/jgp.202012713
发表时间：
2021-03-01
期刊：
The Journal of general physiology
影响因子：
--
作者：
Caremani M;Fusi L;Linari M;Reconditi M;Piazzesi G;Irving TC;Narayanan T;Irving M;Lombardi V;Brunello E
通讯作者：
Brunello E
影响因子：
5.6
作者：
HUXLEY, HE;BROWN, W
通讯作者：
BROWN, W
DOI：
10.1073/pnas.2302837120
发表时间：
2023-05-30
影响因子：
11.1
作者：
Brunello, Elisabetta;Marcucci, Lorenzo;Irving, Malcolm;Fusi, Luca
通讯作者：
Fusi, Luca
影响因子：
2.9
作者：
LYMN, RW;TAYLOR, EW
通讯作者：
TAYLOR, EW
影响因子：
16.6
作者：
Fusi, L.;Brunello, E.;Yan, Z.;Irving, M.
通讯作者：
Irving, M.