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Molecular Interactions and Residues Involved in Force Generation in the T4 Viral DNA Packaging Motor

机译:T4病毒DNA包装电机中涉及力产生的分子相互作用和残基

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Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations. (C) 2014 Elsevier Ltd. All rights reserved.
机译:许多病毒利用分子马达将其基因组包装到预先形成的衣壳中。这些电动机的显着特征是它们能够产生很大的力来驱动DNA转运,以抵抗抵抗DNA限制的熵,静电和弯曲力。基于最近解析的噬菌体T4马达蛋白gp17的结构的模型表明,该马达通过经历从伸展状态到紧凑状态的构象变化,产生很大的力。提议这种转变是由跨gp17 N和C端结构域之间的界面的互补电荷残基之间的静电相互作用驱动的。在这里,我们使用原子分子动力学模拟来详细研究gp17压缩转变中涉及的分子相互作用和残基。我们发现,尽管带电残基之间的静电相互作用对压实的整体自由能变化有显着贡献,但是由不带电残基介导的相互作用同样重要,甚至更为重要。我们在界面上确定了五个带电残基和六个不带电残基,它们在压实过渡中起主要作用,并且还揭示了由这些残基介导的盐桥,范德华和溶剂氢键相互作用,以稳定gp17的紧凑形式。发现在Glu309和Arg494之间形成盐桥特别重要,这与实验表明在Glu309Lys突变后包装中的完全废除相一致。还发现计算出的其他几个残基的贡献与单分子测量对由定点突变引起的DNA转运活性受损的相关性很好。 (C)2014 Elsevier Ltd.保留所有权利。

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