Work Done by Titin Protein Folding Assists Muscle Contraction.
Work Done by Titin Protein Folding Assists Muscle Contraction.
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DOI：
10.1016/j.celrep.2016.01.025
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发表时间：
2016-02-16
期刊：
影响因子：
8.8
通讯作者：
Fernández JM
中科院分区：
文献类型：
--
作者：
Rivas-Pardo JA;Eckels EC;Popa I;Kosuri P;Linke WA;Fernández JM
目前的肌肉收缩理论认为，肌球蛋白马达的动力冲程是驱动收缩肌肉滑动肌丝的机械能的唯一来源。这些模型排除了肌动蛋白，这是人体内最大的蛋白质，它决定了肌肉的被动弹性。在这里，我们表明，在生理肌节长度和 6-8 pN 的力下，肌动蛋白 Ig 结构域的逐步展开/折叠发生在完整肌原纤维的弹性 I 带区域中。我们使用单分子技术证明，未折叠的肌动蛋白 Ig 结构域在低于 10 pN 的力下会经历自发逐步折叠收缩，提供高达 105 zJ 的额外收缩能，该能量大于肌球蛋白马达动力冲程所提供的机械能。因此，似乎不可避免的是，肌联蛋白 Ig 结构域的折叠对于收缩肌肉产生的力来说是一个重要的、但迄今为止尚未被认识到的贡献者。
Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that stepwise unfolding/folding of titin Ig domains occurs in the elastic I band region of intact myofibrils at physiological sarcomere lengths and forces of 6-8 pN. We use single molecule techniques to demonstrate that unfolded titin Ig domains undergo a spontaneous stepwise folding contraction at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, which is larger than the mechanical energy delivered by the power stroke of a myosin motor. Thus, it appears inescapable that folding of titin Ig domains is an important, but so far unrecognized contributor to the force generated by a contracting muscle.