Molecular dynamics studies on troponin (TnI-TnT-TnC) complexes: insight into the regulation of muscle contraction.
Molecular dynamics studies on troponin (TnI-TnT-TnC) complexes: insight into the regulation of muscle contraction.
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DOI：
10.1080/07391102.2010.10507350
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发表时间：
2010-10
影响因子：
4.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Varughese JF;Chalovich JM;Li Y
肌钙蛋白复合体的任何亚基的突变都可能导致严重的疾病。管理这些疾病的合理方法需要了解三个亚基之间的复杂相互作用，这些亚基是正常功能所必需的。对骨骼肌钙蛋白（sTn）和心肌肌钙蛋白（cTn）进行分子动力学（MD）模拟。采用分子力学-广义玻恩表面积（MMGBSA）和互相关技术分析了肌钙蛋白复合物三个组分之间的相互作用和相关运动。TnTH 2螺旋与TnI的两个长螺旋强正相关。TnC C结构域与TnI、TnT呈正相关。在cTn中，TnC的N结构域与TnI、TnT呈负相关，而在sTn中则无相关性。TnC的两个C-结构域钙结合位点动态相关。这两个监管的N-域钙结合位点的TnC动态相关，即使钙结合位点I是功能失调。肌钙蛋白复合物的三个组分之间的强相互作用的残基对和强动态相关的残基对被确定。这些相关的运动是一致的想法，有一个高度的协同性之间的组件的监管复杂的Ca 2+和其他效应。这种方法可能有助于深入了解肌钙蛋白突变导致疾病的机制。有趣的是，一些观察到的导致疾病的突变落在肌钙蛋白区域内，这些区域是强烈相关或相互作用的。
Mutations of any subunit of the troponin complex may lead to serious disorders. Rational approaches to managing these disorders require knowledge of the complex interactions among the three subunits that are required for proper function. Molecular dynamics (MD) simulations were performed for both skeletal (sTn) and cardiac (cTn) troponin. The interactions and correlated motions among the three components of the troponin complex were analyzed using both Molecular Mechanics-Generalized Born Surface Area (MMGBSA) and cross-correlation techniques. The TnTH2 helix was strongly positively correlated with the two long helices of TnI. The C domain of TnC was positively correlated with TnI and TnT. The N domain of TnC was negatively correlated with TnI and TnT in cTn, but not in sTn. The two C-domain calcium-binding sites of TnC were dynamically correlated. The two regulatory N-domain calcium-binding sites of TnC were dynamically correlated, even though the calcium-binding site I is dysfunctional. The strong interaction residue pairs and the strong dynamically correlated residues pairs among the three components of troponin complexes were identified. These correlated motions are consistent with the idea that there is a high degree of cooperativity among the components of the regulatory complex in response to Ca2+ and other effectors. This approach may give insight into the mechanism by which mutations of troponin cause disease. It is interesting that some observed disease causing mutations fall within regions of troponin that are strongly correlated or interacted.
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影响因子：
4.8
作者：
Dweck, David;Hus, Nir;Potter, James D.
通讯作者：
Potter, James D.
DOI：
10.1002/prot.340110305
发表时间：
1991-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
ICHIYE, T;KARPLUS, M
通讯作者：
KARPLUS, M
DOI：
10.1073/pnas.0509181102
发表时间：
2005-12-13
影响因子：
11.1
作者：
Ertz-Berger, BR;He, HM;Tardiff, JC
通讯作者：
Tardiff, JC
DOI：
10.1080/07391102.2008.10507223
发表时间：
2008-08-01
影响因子：
4.4
作者：
Chen, Calvin Yu-Chian;Chen, Yuh-Fung;Tsai, Huei-Yann
通讯作者：
Tsai, Huei-Yann
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML