Toward Understanding the Molecular Bases of Stretch Activation: A STRUCTURAL COMPARISON OF THE TWO TROPONIN C ISOFORMS OF LETHOCERUS.
Toward Understanding the Molecular Bases of Stretch Activation: A STRUCTURAL COMPARISON OF THE TWO TROPONIN C ISOFORMS OF LETHOCERUS.
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DOI：
10.1074/jbc.m116.726646
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发表时间：
2016-07-29
期刊：
影响因子：
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通讯作者：
Pastore A
中科院分区：
文献类型：
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作者：
Sanfelice D;Sanz-Hernández M;de Simone A;Bullard B;Pastore A
肌肉通常是通过与钙感觉蛋白肌钙蛋白C结合而激活的，肌钙蛋白C是肌钙蛋白复合体的三个组成部分之一。然而，在心脏和昆虫飞行中，肌肉的激活也是由机械压力引起的。人们对这种钙非依赖性激活的分子基础知之甚少。在巨型水虫Lethocerus中，有两种肌钙蛋白-C亚型，称为F1和F2，在激活肌肉方面具有不同的作用。Lethocerus是一种巨大的水虫，由于其巨大的肌肉纤维，它经常被用作模型系统。有人认为，这可以通过结构特征的不同或与其他蛋白质相互作用的不同来解释。在这里，我们比较了这两种蛋白质的结构和动力学性质，并展示了它们的不同之处。我们还绘制了F2亚型与其天然伴侣肌钙蛋白-I序列上的多肽之间的相互作用图。我们的数据使我们能够建立肌钙蛋白复合体的模型，并最终可能有助于理解F1和F2亚型的特殊功能和拉伸激活的分子机制。
Muscles are usually activated by calcium binding to the calcium sensory protein troponin-C, which is one of the three components of the troponin complex. However, in cardiac and insect flight muscle activation is also produced by mechanical stress. Little is known about the molecular bases of this calcium-independent activation. In Lethocerus, a giant water bug often used as a model system because of its large muscle fibers, there are two troponin-C isoforms, called F1 and F2, that have distinct roles in activating the muscle. It has been suggested that this can be explained either by differences in structural features or by differences in the interactions with other proteins. Here we have compared the structural and dynamic properties of the two proteins and shown how they differ. We have also mapped the interactions of the F2 isoform with peptides spanning the sequence of its natural partner, troponin-I. Our data have allowed us to build a model of the troponin complex and may eventually help in understanding the specialized function of the F1 and F2 isoforms and the molecular mechanism of stretch activation.