Quantitative Study of the Chiral Organization of the Phage Genome Induced by the Packaging Motor
Quantitative Study of the Chiral Organization of the Phage Genome Induced by the Packaging Motor
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DOI：
10.1016/j.bpj.2020.03.030
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发表时间：
2020-05-05
影响因子：
3.4
通讯作者：
Vazquez, Mariel
中科院分区：
文献类型：
--
作者：
Cruz, Brian;Zhu, Zihao;Vazquez, Mariel
DNA转位的分子马达在自然界中无处不在。在双链DNA噬菌体的形态发生过程中，分子马达驱动蛋白质衣壳内的病毒基因组。已经提出了几个模型的三维几何形状的包装基因组，但很少有人知道的签名的分子包装电机。例如，生物物理实验表明，在某些系统中，DNA在包装反应期间会旋转，但大多数当前的生物物理模型都未能纳入这一特性。此外，包括轮换机制在内的研究得出了相互矛盾的结论。在这项研究中，我们比较了包装电机的不同可能的机制所施加的几何签名：旋转，革命，旋转与革命。我们使用先前提出的动力学蒙特卡罗模型的电机，结合布朗动力学模拟的DNA模拟确定性和随机电机模型。我们发现，旋转是必要的积累DNA扭曲和手性组织的基因组。我们观察到，虽然在包装反应的初始步骤中，基因组的扭转应变是通过分子的旋转释放的，但在后期阶段，它是通过扭动的积累释放的。我们认为，分子马达起着关键的作用，在确定最终结构的bacteriophages.Significance病毒基因组的三维组织中的bacteriophages.Significance决定了病毒感染的关键功能方面。在双链DNA噬菌体中，包装反应是由分子马达进行的，该分子马达驱动其蛋白质衣壳内的病毒基因组。在这项研究中，我们确定的包装电机的病毒基因组的最终包装配置的贡献。使用先前提出的动力学蒙特卡罗模型的电机，结合布朗动力学模拟的DNA，我们发现，旋转的DNA分子的电机在包装反应诱导手性包装。
Molecular motors that translocate DNA are ubiquitous in nature. During morphogenesis of double-stranded DNA bacteriophages, a molecular motor drives the viral genome inside a protein capsid. Several models have been proposed for the three-dimensional geometry of the packaged genome, but very little is known of the signature of the molecular packaging motor. For instance, biophysical experiments show that in some systems, DNA rotates during the packaging reaction, but most current biophysical models fail to incorporate this property. Furthermore, studies including rotation mechanisms have reached contradictory conclusions. In this study, we compare the geometrical signatures imposed by different possible mechanisms for the packaging motors: rotation, revolution, and rotation with revolution. We used a previously proposed kinetic Monte Carlo model of the motor, combined with Brownian dynamics simulations of DNA to simulate deterministic and stochastic motor models. We find that rotation is necessary for the accumulation of DNA writhe and for the chiral organization of the genome. We observe that although in the initial steps of the packaging reaction, the torsional strain of the genome is released by rotation of the molecule, in the later stages, it is released by the accumulation of writhe. We suggest that the molecular motor plays a key role in determining the final structure of the encapsidated genome in bacteriophages.SIGNIFICANCE The three-dimensional organization of viral genomes determines key functional aspects of viral infection. In double-stranded DNA bacteriophages, the packaging reaction is carried out by a molecular motor that drives the viral genome inside its protein capsid. In this study, we determine the contribution of the packaging motor to the final packaged configuration of the viral genome. Using a previously proposed kinetic Monte Carlo model of the motor, combined with Brownian dynamics simulations of DNA, we find that rotation of the DNA molecule by the motor during the packaging reaction induces chiral packing.