title: DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos.
abstract: 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.
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516.|Howard Hughes Medical Institute, Yale University, New Haven, CT 06516.
authors: Ivan V
authors: IV
authors: Surovtsev
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516.|Howard Hughes Medical Institute, Yale University, New Haven, CT 06516.
authors: Manuel
authors: M
authors: Campos
authors: Microbial Sciences Institute, Yale University, West Haven, CT 06517; christine.jacobs-wagner@yale.edu.|Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06516.|Howard Hughes Medical Institute, Yale University, New Haven, CT 06516.|Department of Microbial Pathogenesis, Yale Medical School, New Haven, CT 06516.
authors: Christine
authors: C
authors: Jacobs-Wagner
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D019915:DNA Primase / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C541712:ParA protein, E coli; D000255:Adenosine Triphosphate; D019915:DNA Primase; C121791:dnaG protein, E coli
keywords: ParA/B system; active transport; intracellular patterning; mathematical model; partitioning