Surovtsev Ivan V, Campos Manuel, Jacobs-Wagner Christine
Microbial Sciences Institute, Yale University, West Haven, CT 06517.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516.
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):E7268-E7276. doi: 10.1073/pnas.1616118113. Epub 2016 Oct 31.
Spatial ordering of macromolecular components inside cells is important for cellular physiology and replication. In bacteria, ParA/B systems are known to generate various intracellular patterns that underlie the transport and partitioning of low-copy-number cargos such as plasmids. ParA/B systems consist of ParA, an ATPase that dimerizes and binds DNA upon ATP binding, and ParB, a protein that binds the cargo and stimulates ParA ATPase activity. Inside cells, ParA is asymmetrically distributed, forming a propagating wave that is followed by the ParB-rich cargo. These correlated dynamics lead to cargo oscillation or equidistant spacing over the nucleoid depending on whether the cargo is in single or multiple copies. Currently, there is no model that explains how these different spatial patterns arise and relate to each other. Here, we test a simple DNA-relay model that has no imposed asymmetry and that only considers the ParA/ParB biochemistry and the known fluctuating and elastic dynamics of chromosomal loci. Stochastic simulations with experimentally derived parameters demonstrate that this model is sufficient to reproduce the signature patterns of ParA/B systems: the propagating ParA gradient correlated with the cargo dynamics, the single-cargo oscillatory motion, and the multicargo equidistant patterning. Stochasticity of ATP hydrolysis breaks the initial symmetry in ParA distribution, resulting in imbalance of elastic force acting on the cargo. Our results may apply beyond ParA/B systems as they reveal how a minimal system of two players, one binding to DNA and the other modulating this binding, can transform directionally random DNA fluctuations into directed motion and intracellular patterning.
细胞内大分子成分的空间排列对于细胞生理和复制至关重要。在细菌中，已知ParA/B系统会产生各种细胞内模式，这些模式是低拷贝数货物（如质粒）运输和分配的基础。ParA/B系统由ParA和ParB组成，ParA是一种ATP酶，在结合ATP时会二聚化并结合DNA，ParB是一种结合货物并刺激ParA ATP酶活性的蛋白质。在细胞内，ParA呈不对称分布，形成一个传播波，随后是富含ParB的货物。这些相关的动力学导致货物在类核上振荡或等距分布，这取决于货物是单拷贝还是多拷贝。目前，尚无模型能够解释这些不同的空间模式是如何产生以及它们之间的关系。在这里，我们测试了一个简单的DNA中继模型，该模型没有强加的不对称性，仅考虑ParA/ParB生物化学以及染色体位点已知的波动和弹性动力学。用实验得出的参数进行的随机模拟表明，该模型足以重现ParA/B系统的标志性模式：与货物动力学相关的传播ParA梯度、单货物振荡运动和多货物等距模式。ATP水解的随机性打破了ParA分布中的初始对称性，导致作用于货物的弹力失衡。我们的结果可能适用于ParA/B系统之外的情况，因为它们揭示了一个由两个参与者组成的最小系统，一个与DNA结合，另一个调节这种结合，如何将定向随机的DNA波动转化为定向运动和细胞内模式。
