Cruz Brian, Zhu Zihao, Calderer Carme, Arsuaga Javier, Vazquez Mariel
Department of Mathematics, University of California, Berkeley, California.
Department of Microbiology and Molecular Genetics, University of California at Davis, Davis, California.
Biophys J. 2020 May 5;118(9):2103-2116. doi: 10.1016/j.bpj.2020.03.030. Epub 2020 Apr 14.
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.
在自然界中，能够转运DNA的分子马达普遍存在。在双链DNA噬菌体的形态发生过程中，一种分子马达将病毒基因组驱动到蛋白质衣壳内部。针对包装好的基因组的三维几何结构，已经提出了几种模型，但对于分子包装马达的特征却知之甚少。例如，生物物理实验表明，在某些系统中，DNA在包装反应过程中会发生旋转，但目前大多数生物物理模型都未能纳入这一特性。此外，包括旋转机制在内的研究得出了相互矛盾的结论。在本研究中，我们比较了包装马达不同可能机制所施加的几何特征：旋转、公转以及旋转与公转相结合。我们使用了先前提出的马达动力学蒙特卡洛模型，并结合DNA的布朗动力学模拟，来模拟确定性和随机性马达模型。我们发现，旋转对于DNA缠绕的积累以及基因组的手性组织是必要的。我们观察到，虽然在包装反应的初始阶段，基因组的扭转应变通过分子的旋转得以释放，但在后期阶段，它是通过缠绕的积累来释放的。我们认为，分子马达在决定噬菌体中衣壳化基因组的最终结构方面起着关键作用。
