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首页> 外文期刊>Journal of Molecular and Cellular Cardiology >Regulatory domain of troponin moves dynamically during activation of cardiac muscle
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Regulatory domain of troponin moves dynamically during activation of cardiac muscle

机译：肌钙蛋白的调节域在心肌激活过程中动态移动

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Heart muscle is activated by Ca2+ to generate force and shortening, and the signaling pathway involves allosteric mechanisms in the thin filament. Knowledge about the structure-function relationship among proteins in the thin filament is critical in understanding the physiology and pathology of the cardiac function, but remains obscure. We investigate the conformation of the cardiac troponin (Tn) on the thin filament and its response to Ca2+ activation and propose a molecular mechanism for the regulation of cardiac muscle contraction by Tn based uniquely on information from in situ protein domain orientation. Polarized fluorescence from bifunctional rhodamine is used to determine the orientation of the major component of Tn core domain on the thin filaments of cardiac muscle. We show that the C-terminal lobe of TnC (CTnC) does not move during activation, suggesting that CTnC, together with the coiled coil formed by the TnI and TnT chains (IT arm), acts as a scaffold that holds N-terminal lobe of TnC (NTnC) and the actin binding regions of troponin I. The NTnC, on the other hand, exhibits multiple orientations during both diastole and systole. By combining the in situ orientation data with published in vitro measurements of intermolecular distances, we construct a model for the in situ structure of the thin filament. The conformational dynamics of NTnC plays an important role in the regulation of cardiac muscle contraction by moving the C-terminal region of TnI from its actin-binding inhibitory location and enhancing the movement of tropomyosin away from its inhibitory position. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://c-reativecommons.orylicenses/by-nc-nd/3.0/).
机译：心肌被Ca2 +激活以产生力并缩短，信号传导途径涉及细丝中的变构机制。关于细丝中蛋白质之间的结构-功能关系的知识对于理解心脏功能的生理学和病理学至关重要，但仍然晦涩难懂。我们研究细丝上的心肌肌钙蛋白（Tn）的构象及其对Ca2 +激活的反应，并基于原位蛋白域定向信息，提出了一种通过Tn调节心肌收缩的分子机制。来自双功能罗丹明的偏振荧光用于确定心肌细丝上Tn核心域主要成分的方向。我们显示TnC（CTnC）的C末端叶在激活过程中不会移动，这表明CTnC以及由TnI和TnT链（IT臂）形成的螺旋状线圈，充当持有N末端叶的支架TnC（NTnC）和肌钙蛋白I的肌动蛋白结合区。另一方面，NTnC在舒张期和收缩期均表现出多种取向。通过结合原位取向数据与已公布的分子间距离的体外测量结果，我们构建了细丝原位结构的模型。 NTnC的构象动力学通过将TnI的C端区域从其肌动蛋白结合抑制位置移开并增强原肌球蛋白从其抑制位置移出，在调节心肌收缩中起重要作用。 （C）2014作者。由Elsevier Ltd.发行。这是CC BY-NC-ND许可（http：//c-reativecommons.orylicenses/by-nc-nd/3.0/）下的开放访问文章。

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