Molecular interactions between mitochondrial membrane proteins and the C-terminal domain of PB1-F2: an in silico approach
Molecular interactions between mitochondrial membrane proteins and the C-terminal domain of PB1-F2: an in silico approach
复制标题
DOI：
10.1007/s00894-009-0555-5
复制
发表时间：
2010-03-01
影响因子：
2.2
通讯作者：
Khan, Asad U.
中科院分区：
文献类型：
--
作者：
Danishuddin, Mohd;Khan, Shahper N.;Khan, Asad U.
PB1-F2是最近发现的一种甲型流感病毒蛋白，它通过与两种线粒体膜蛋白结合诱导细胞凋亡，即VDAC1（外膜）和ANT3（内膜）。这种结合机制的知识可以为设计针对这种蛋白质的新型抑制剂提供帮助。因此，为了更好地了解这些相互作用，我们开展了这项研究，对高致病性甲型流感病毒H5N1亚型的PB1-F2蛋白进行了建模。此外，还建立了人ANT3的模型。采用计算机模拟的方法，阐述了PB1-F2蛋白c端区与VDAC1和ANT3分子相互作用的动力学过程。结果表明，PB1-F2蛋白的12个氨基酸与VDAC1的22个氨基酸形成疏水接触。其中，Leu64、Arg75和Val76被发现对线粒体靶向至关重要。在PB1-F2-ANT3配合物中，发现ANT3的14个氨基酸与PB1-F2的9个氨基酸发生疏水接触。此外，在PB1-F2/VDAC1和PB1-F2/ANT3配合物中预测了两个氢键。这项研究揭示了pb1 - f2诱导细胞凋亡所需的分子相互作用，并为未来的研究提出了一个假设模型。
PB1-F2 is a recently described influenza A viral protein that induces apoptosis by binding with two mitochondrial membrane proteins, i.e. VDAC1 (outer membrane) and ANT3 (inner membrane). Knowledge of this binding mechanism could provide insights that would aid in the design of novel inhibitors against this protein. Therefore, to better understand these interactions, we have undertaken this study to model the PB1-F2 protein of the highly pathogenic influenza A virus subtype H5N1. Moreover, a model of human ANT3 was also established. The dynamics of the molecular interactions between the C-terminal region of PB1-F2 protein and VDAC1 and ANT3 were expounded by employing an in silico approach. Our results suggest the involvement of 12 amino acids of PB1-F2 protein, which form hydrophobic contacts with 22 amino acids of VDAC1. Of these, Leu64, Arg75 and Val76 were found to be crucial for mitochondrial targetting. In the case of the PB1-F2-ANT3 complex, 14 amino acids of ANT3 were found to make hydrophobic contacts with 9 amino acids of PB1-F2. Furthermore, two hydrogen bonds were predicted in both complexes PB1-F2/VDAC1 and PB1-F2/ANT3. This study reveals the molecular interactions required for PB1-F2-induced apoptosis and suggests a hypothetical model for future study.