title: Condensation and localization of the partitioning protein ParB on the bacterial chromosome.
abstract: The ParABS system mediates chromosome segregation and plasmid partitioning in many bacteria. As part of the partitioning mechanism, ParB proteins form a nucleoprotein complex at parS sites. The biophysical basis underlying ParB-DNA complex formation and localization remains elusive. Specifically, it is unclear whether ParB spreads in 1D along DNA or assembles into a 3D protein-DNA complex. We show that a combination of 1D spreading bonds and a single 3D bridging bond between ParB proteins constitutes a minimal model for a condensed ParB-DNA complex. This model implies a scaling behavior for ParB-mediated silencing of parS-flanking genes, which we confirm to be satisfied by experimental data from P1 plasmids. Furthermore, this model is consistent with experiments on the effects of DNA roadblocks on ParB localization. Finally, we show experimentally that a single parS site is necessary and sufficient for ParB-DNA complex formation in vivo. Together with our model, this suggests that ParB binding to parS triggers a conformational switch in ParB that overcomes a nucleation barrier. Conceptually, the combination of spreading and bridging bonds in our model provides a surface tension ensuring the condensation of the ParB-DNA complex, with analogies to liquid-like compartments such as nucleoli in eukaryotes.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics,Joseph Henry Laboratories of Physics, and.
authors.forename: Chase P
authors.initials: CP
authors.lastname: Broedersz
authors.affiliation: Departments of Microbiology and Immunobiology and.
authors.forename: Xindan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physics, Ben-Gurion University, Beer Sheva 84105, Israel.
authors.forename: Yigal
authors.initials: Y
authors.lastname: Meir
authors.affiliation: Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; and.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Loparo
authors.affiliation: Departments of Microbiology and Immunobiology and.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Rudner
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics,Department of Molecular Biology, Princeton University, Princeton, NJ 08544; wingreen@princeton.edu.
authors.forename: Ned S
authors.initials: NS
authors.lastname: Wingreen
mesh_terms: D000465:Algorithms; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology*; D001665:Binding Sites; D002876:Chromosomes, Bacterial / Q000737:chemistry*; D004269:DNA, Bacterial / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry; D020868:Gene Silencing; D023281:Genomics; D049452:Green Fluorescent Proteins / Q000737:chemistry; D007700:Kinetics; D009010:Monte Carlo Method; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software; D013696:Temperature
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; C052883:chromosome partition proteins, bacterial; D049452:Green Fluorescent Proteins
keywords: par system; protein localization; protein-DNA condensate