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bioRxiv · 10.1101/2022.12.01.518708

Partition complex structure can arise from sliding and bridging of ParB dimers

Connolley, L.·Schnabel, L.·Thanbichler, M.·Murray, S. M.
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Abstract

Chromosome segregation is vital for cell replication and in many bacteria is controlled by the ParABS system. A key part of this machinery is the association of ParB proteins to the parS-containing centromeric region to form the partition complex. Despite much work, the formation and structure of this nucleoprotein complex has remained unclear. However, it was recently discovered that CTP binding allows ParB dimers to entrap and slide along the DNA, as well as leading to more efficient condensation through ParB-mediated DNA bridging. Here, we use semi-flexible polymer simulations to show how these properties of sliding and bridging can explain partition complex formation. We find that transient ParB bridges can organise the DNA into either a globular state or into hairpins and helical structures, depending on the bridge lifetime. In separate stochastic simulations, we show that ParB sliding reproduces the experimentally measured multi-peaked binding profile of Caulobacter crescentus, indicating that bridging and other potential roadblocks are sufficiently short-lived that they do not hinder ParB spreading. Indeed, upon coupling the two simulation frameworks into a unified sliding and bridging model, we find that short-lived ParB bridges do not hinder ParB sliding and the model can reproduce both the ParB binding profile as well as the condensation of the nucleoprotein complex. Overall, our model clarifies the mechanism of partition complex formation and predicts its fine structure. We speculate that the DNA hairpins produced by ParB bridging underlie the secondary function of ParB to load the Structural Maintenance of Chromosome (SMC) complex onto the DNA.

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Connolley, L., Schnabel, L., Thanbichler, M., Murray, S. M.. 2022-12-02. Partition complex structure can arise from sliding and bridging of ParB dimers. https://doi.org/10.1101/2022.12.01.518708

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