Arnold Sommerfeld Center for Theoretical Physics and Center for NanoScience, Department of Physics, Ludwig-Maximilians-Universität München, Munich, Germany.
PLoS Comput Biol. 2018 Aug 13;14(8):e1006358. doi: 10.1371/journal.pcbi.1006358. eCollection 2018 Aug.
Precise positioning of the cell division site is essential for the correct segregation of the genetic material into the two daughter cells. In the bacterium Myxococcus xanthus, the proteins PomX and PomY form a cluster on the chromosome that performs a biased random walk to midcell and positively regulates cell division there. PomZ, an ATPase, is necessary for tethering of the cluster to the nucleoid and regulates its movement towards midcell. It has remained unclear how the cluster dynamics change when the biochemical parameters, such as the attachment rates of PomZ dimers to the nucleoid and the cluster, the ATP hydrolysis rate of PomZ or the mobility of PomZ interacting with the nucleoid and cluster, are varied. To answer these questions, we investigate a one-dimensional model that includes the nucleoid, the Pom cluster and PomZ proteins. We find that a mechanism based on the diffusive PomZ fluxes on the nucleoid into the cluster can explain the latter's midnucleoid localization for a broad parameter range. Furthermore, there is an ATP hydrolysis rate that minimizes the time the cluster needs to reach midnucleoid. If the dynamics of PomZ on the nucleoid is slow relative to the cluster's velocity, we observe oscillatory cluster movements around midnucleoid. To understand midnucleoid localization, we developed a semi-analytical approach that dissects the net movement of the cluster into its components: the difference in PomZ fluxes into the cluster from either side, the force exerted by a single PomZ dimer on the cluster and the effective friction coefficient of the cluster. Importantly, we predict that the Pom cluster oscillates around midnucleoid if the diffusivity of PomZ on the nucleoid is reduced. A similar approach to that applied here may also prove useful for cargo localization in ParABS systems.
细胞分裂位点的精确定位对于将遗传物质正确分配到两个子细胞中至关重要。在黄杆菌（Myxococcus xanthus）中，蛋白质 PomX 和 PomY 在染色体上形成一个簇，该簇进行偏向随机游动到达细胞中部，并在那里正向调节细胞分裂。ATP 酶 PomZ 对于将簇固定在核区并调节其向细胞中部的运动是必要的。当生化参数（例如 PomZ 二聚体与核区和簇的附着率、PomZ 的 ATP 水解速率或与核区和簇相互作用的 PomZ 的流动性）发生变化时，簇动力学如何变化仍不清楚。为了回答这些问题，我们研究了一个包括核区、Pom 簇和 PomZ 蛋白的一维模型。我们发现，基于 PomZ 在核区扩散通量进入簇的机制可以解释后者在广泛的参数范围内的核中部定位。此外，存在一个最小化簇到达核中部所需时间的 ATP 水解速率。如果 PomZ 在核区的动力学相对于簇的速度较慢，我们会观察到簇围绕核中部的振荡运动。为了理解核中部定位，我们开发了一种半解析方法，将簇的净运动分解为其组成部分：来自两侧的 PomZ 进入簇的通量差异、单个 PomZ 二聚体对簇的力以及簇的有效摩擦系数。重要的是，如果 PomZ 在核区的扩散性降低，我们预测 Pom 簇将在核中部周围振荡。这里应用的类似方法也可能对 ParABS 系统中的货物定位证明有用。
