Insight into conformational change for 14-3-3σ protein by molecular dynamics simulation.
Insight into conformational change for 14-3-3σ protein by molecular dynamics simulation.
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通过分子动力学模拟洞察 14-3-3Ï 蛋白质的构象变化
DOI：
10.3390/ijms15022794
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发表时间：
2014-02-18
影响因子：
5.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Hu G;Li H;Liu JY;Wang J
14-3-3σ是一个高度保守的14-3-3蛋白家族成员，在人类癌症中起着双刃剑的作用。以往的报道表明，14-3-3蛋白可能处于开放或关闭状态。在本工作中，我们基于80 ns的分子动力学(MD)模拟发现，APO-14-3-3σ与磷酸肽结合的14-3-3σ络合物相比处于开放状态。14-3-3-σ的两个单体在开放状态和关闭状态下的相互作用是相同的。在开放和闭合状态下，参与二聚化的螺旋A到D都是稳定的。但在螺旋E和F上发现了很大的差异。APO-14-3-3σ中螺旋E和G之间的疏水接触和氢键不同于结合的14-3-3σ复合体。抑制和突变(Arg56或Arg129为丙氨酸)的MD模拟表明，4个残基(Lys49、Arg56、Arg129和Tyr130)的构象可能对保持14-3-3-3σ蛋白的开放或关闭状态起重要作用。这些结果将有助于评价14-3-3σ蛋白的结构与功能的关系。
14-3-3σ is a member of a highly conserved family of 14-3-3 proteins that has a double-edged sword role in human cancers. Former reports have indicated that the 14-3-3 protein may be in an open or closed state. In this work, we found that the apo-14-3-3σ is in an open state compared with the phosphopeptide bound 14-3-3σ complex which is in a more closed state based on our 80 ns molecular dynamics (MD) simulations. The interaction between the two monomers of 14-3-3σ in the open state is the same as that in the closed state. In both open and closed states, helices A to D, which are involved in dimerization, are stable. However, large differences are found in helices E and F. The hydrophobic contacts and hydrogen bonds between helices E and G in apo-14-3-3σ are different from those in the bound 14-3-3σ complex. The restrained and the mutated (Arg56 or Arg129 to alanine) MD simulations indicate that the conformation of four residues (Lys49, Arg56, Arg129 and Tyr130) may play an important role to keep the 14-3-3σ protein in an open or closed state. These results would be useful to evaluate the 14-3-3σ protein structure-function relationship.
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影响因子：
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