Troponin structure: its modulation by Ca(2+) and phosphorylation studied by molecular dynamics simulations.
Troponin structure: its modulation by Ca(2+) and phosphorylation studied by molecular dynamics simulations.
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肌钙蛋白结构：通过分子动力学模拟研究 Ca(2 ) 的调节和磷酸化。
DOI：
10.1039/c6cp02610a
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
I. Gould
中科院分区：
文献类型：
--
作者：
Juan Eiros Zamora;M. Papadaki;A. Messer;Steven B Marston;I. Gould
Ca（2+）激活状态下人心肌肌钙蛋白分子（cTnI）的唯一可用晶体结构不包括关键片段，包括cTnI抑制亚基（cTnI）的N-末端。我们已经应用全原子分子动力学（MD）模拟研究的结构和动力学的cTnI，无论是在非磷酸化和双磷酸化的状态在Ser 23/Ser 24。我们在含有人序列cTnC（1-161）、cTnI（1-171）和cTnT（212-298）（包括晶体结构中不存在的残基）的419个氨基酸的cTn模型上，对野生型（WT）cTn（6.5 μs）和双磷酸化（SP23/SP24）cTn（9 μs）进行了多次微秒MD模拟。我们已经将我们的结果与以前的计算研究进行了比较，并证明了需要更长的模拟和至少25 μ m的水盒来对天然和双磷酸化状态下的有趣构象变化进行采样。由于在模型中引入了之前研究中缺失的cTnT C-末端，导致cTnC-cTnI相互作用发生改变，从而导致cTnD动力学改变。我们还表明，磷酸化不会增加cTn的波动，其对蛋白质-蛋白质相互作用的影响不能以显着的方式进行评估。最后，我们提出，磷酸化可以引起钙（2+）的损失，通过稳定的协调距离cTnC的EF手II残基，特别是Ser 69。
The only available crystal structure of the human cardiac troponin molecule (cTn) in the Ca(2+) activated state does not include crucial segments, including the N-terminus of the cTn inhibitory subunit (cTnI). We have applied all-atom molecular dynamics (MD) simulations to study the structure and dynamics of cTn, both in the unphosphorylated and bis-phosphorylated states at Ser23/Ser24 of cTnI. We performed multiple microsecond MD simulations of wild type (WT) cTn (6, 5 μs) and bisphosphorylated (SP23/SP24) cTn (9 μs) on a 419 amino acid cTn model containing human sequence cTnC (1-161), cTnI (1-171) and cTnT (212-298), including residues not present in the crystal structure. We have compared our results to previous computational studies, and proven that longer simulations and a water box of at least 25 Å are needed to sample the interesting conformational shifts both in the native and bis-phosphorylated states. As a consequence of the introduction into the model of the C-terminus of cTnT that was missing in previous studies, cTnC-cTnI interactions that are responsible for the cTn dynamics are altered. We have also shown that phosphorylation does not increase cTn fluctuations, and its effects on the protein-protein interaction profiles cannot be assessed in a significant way. Finally, we propose that phosphorylation could provoke a loss of Ca(2+) by stabilizing out-of-coordination distances of the cTnC's EF hand II residues, and in particular Ser 69.
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DOI：
10.1016/j.bbrc.2007.12.114
发表时间：
2008-04-25
影响因子：
3.1
作者：
Solaro, R. John;Rosevear, Paul;Kobayashi, Tomoyoshi
通讯作者：
Kobayashi, Tomoyoshi
放松状态下心肌细丝上肌钙蛋白的三维组织。
影响因子：
3.4
作者：
Yang,Shixin;Barbu-Tudoran,Lucian;Orzechowski,Marek;Craig,Roger;Trinick,John;White,Howard;Lehman,William
通讯作者：
Lehman,William
心肌肌钙蛋白 C L57Q 和 I61Q Ca(2 ) 脱敏变体的结构和功能后果。
影响因子：
3.9
作者：
Wang,Dan;McCully,MichelleE;Luo,Zhaoxiong;McMichael,Jonathan;Tu,An-Yue;Daggett,Valerie;Regnier,Michael
通讯作者：
Regnier,Michael
影响因子：
2.9
作者：
Spyracopoulos, L;Li, MX;Sykes, BD
通讯作者：
Sykes, BD