Cooperative [Ca2+]-Dependent Regulation of the Rate of Myosin Binding to Actin: Solution Data and the Tropomyosin Chain Model
Cooperative [Ca2+]-Dependent Regulation of the Rate of Myosin Binding to Actin: Solution Data and the Tropomyosin Chain Model
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DOI：
10.1016/j.bpj.2011.04.020
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发表时间：
2011-06-08
影响因子：
3.4
通讯作者：
Smith, David
中科院分区：
文献类型：
--
作者：
Geeves, Michael;Griffiths, Hugh;Smith, David
钙对肌肉收缩的调节涉及肌动蛋白丝、肌球蛋白-S1、原肌球蛋白（Tm）和肌钙蛋白（Tn）之间的相互作用。我们已经扩展了我们以前的模型，其中TmTn调节单元被视为一个连续的灵活的链，并将其应用到瞬态动力学数据。我们已经测量了肌球蛋白-S1结合肌动蛋白-Tm-Tn丝在溶液中的时间过程中，在不同的钙水平与[肌动蛋白]/[肌球蛋白]的比例为10和0.1，表现出适度的减缓[Ca 2 +]减少，并在低钙的滞后期。这些观察结果可以解释，如果肌球蛋白结合肌动蛋白在两个步骤，其中第一步是限速和阻断TmTnl在低钙，第二步是快速的，可逆的，并控制耦合原肌球蛋白-肌钙蛋白单位的相邻配置。该模型可以描述所观察到的肌球蛋白结合反应的钙依赖性，并预测协同钙结合到TnC与肌动蛋白和Ca-TnC之间的竞争TnI的结合。在肌肉中的细丝调节理论的影响进行了讨论。
The regulation of muscle contraction by calcium involves interactions among actin filaments, myosin-S1, tropomyosin (Tm), and troponin (Tn). We have extended our previous model in which the TmTn regulatory units are treated as a continuous flexible chain, and applied it to transient kinetic data. We have measured the time course of myosin-S1 binding to actin-Tm-Tn filaments in solution at various calcium levels with [actin]/[myosin] ratios of 10 and 0.1, which exhibit modest slowing as [Ca2+] is reduced and a lag phase at low calcium. These observations can be explained if myosin binds to actin in two steps, where the first step is rate-limiting and blocked by TmTnl at low calcium, and the second step is fast, reversible, and controlled by the neighboring configuration of coupled tropomyosin-troponin units. The model can describe the calcium dependence of the observed myosin binding reactions and predicts cooperative calcium binding to TnC with competition between actin and Ca-TnC for the binding of Tnl. Implications for theories of thin-filament regulation in muscle are discussed.