Theoretical elucidation of the origin for assembly of the DAP12 dimer with only one NKG2C in the lipid membrane.
Theoretical elucidation of the origin for assembly of the DAP12 dimer with only one NKG2C in the lipid membrane.
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DOI：
10.1021/jp312375g
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
Hui Sun;Huiying Chu;Ting Fu;Hujun Shen;Guohui Li
中科院分区：
文献类型：
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作者：
Hui Sun;Huiying Chu;Ting Fu;Hujun Shen;Guohui Li
本研究通过密度泛函理论（DFT）计算和分子动力学（MD）模拟，从电子性质和动力学结构两个方面详细研究了激活免疫受体复合体中只有一个NKG2C的DAP12二聚体的组装起源。在DFT计算中，我们通过分析静电电位和前沿分子轨道（FMOs）研究了NKG2C（TM）与DAP12（TM）二聚体和DAP12(TM)-DAP12(TM)-NKG2C（TM）复合物的聚集能力；在MD模拟中，我们主要研究了DAP12(TM)-DAP12(TM)-NKG2C（TM）复合物及其突变体的动态结构，以及由两个DAP12（TM）和两个NKG2C（TM）螺旋组成的不受任何限制的四聚体复合物。通过对静电势、FMOs和动态结构的研究，我们在一定程度上为实验观察到只有一个NKG2C可以与DAP12同二聚体结合提供了合理的解释。本文的理论结果有望为进一步研究受体与信号亚基之间的组装提供有价值的信息。
In this work, we have investigated in details the origin of the assembly of the DAP12 dimer with only one NKG2C in the activating immunoreceptor complex from thew two aspects of electronic properties and dynamic structures by performing density functional theory (DFT) calculations and molecular dynamics (MD) simulations. In the DFT calculations, we studied the aggregation ability of the NKG2C(TM) with the DAP12(TM) dimer and the DAP12(TM)-DAP12(TM)-NKG2C(TM) complex by analyzing the electrostatic potentials and frontier molecular orbitals (FMOs), and in the MD simulations we mainly investigated the dynamic structures of the DAP12(TM)-DAP12(TM)-NKG2C(TM) complex and its mutants, as well as the tetramer complex consisting of two DAP12(TM) and two NKG2C(TM) helixes without any restriction. Through the studies of the electrostatic potential, the FMOs, and the dynamic structures, we have provided reasonable explanations to some extent for the experimental observation that only one NKG2C can associate with the DAP12 homodimer. The present theoretical results are expected to give valuable information for further studying the assembly between receptors and signaling subunits.