title: Stochastic Self-Assembly of ParB Proteins Builds the Bacterial DNA Segregation Apparatus.
abstract: Many canonical processes in molecular biology rely on the dynamic assembly of higher-order nucleoprotein complexes. In bacteria, the assembly mechanism of ParABS, the nucleoprotein super-complex that actively segregates the bacterial chromosome and many plasmids, remains elusive. We combined super-resolution microscopy, quantitative genome-wide surveys, biochemistry, and mathematical modeling to investigate the assembly of ParB at the centromere-like sequences parS. We found that nearly all ParB molecules are actively confined around parS by a network of synergistic protein-protein and protein-DNA interactions. Interrogation of the empirically determined, high-resolution ParB genomic distribution with modeling suggests that instead of binding only to specific sequences and subsequently spreading, ParB binds stochastically around parS over long distances. We propose a new model for the formation of the ParABS partition complex based on nucleation and caging: ParB forms a dynamic lattice with the DNA around parS. This assembly model and approach to characterizing large-scale, dynamic interactions between macromolecules may be generalizable to many unrelated machineries that self-assemble in superstructures.
authors.affiliation: Laboratoire de Microbiologie et Génétique Moléculaires, Centre National de la Recherche Scientifique, 31062 Toulouse, France; Laboratoire de Microbiologie et Génétique Moléculaires, Université de Toulouse 3, 31062 Toulouse, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Sanchez
authors.affiliation: Centre de Biochimie Structurale, Institut National de la Santé et la Recherche Médicale U554, Centre National de la Recherche Scientifique UMR5048, Université de Montpellier, 34090 Montpellier, France.
authors.forename: Diego I
authors.initials: DI
authors.lastname: Cattoni
authors.affiliation: Laboratoire de Microbiologie et Génétique Moléculaires, Centre National de la Recherche Scientifique, 31062 Toulouse, France; Laboratoire de Microbiologie et Génétique Moléculaires, Université de Toulouse 3, 31062 Toulouse, France; Laboratoire Charles Coulomb, UMR5221 CNRS-Université de Montpellier, 34095 Montpellier, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Walter
authors.affiliation: Laboratoire de Microbiologie et Génétique Moléculaires, Centre National de la Recherche Scientifique, 31062 Toulouse, France; Laboratoire de Microbiologie et Génétique Moléculaires, Université de Toulouse 3, 31062 Toulouse, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rech
authors.affiliation: Laboratoire Charles Coulomb, UMR5221 CNRS-Université de Montpellier, 34095 Montpellier, France; Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235 CNRS-Université de Montpellier, 34095 Montpellier, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Parmeggiani
authors.affiliation: Centre de Biochimie Structurale, Institut National de la Santé et la Recherche Médicale U554, Centre National de la Recherche Scientifique UMR5048, Université de Montpellier, 34090 Montpellier, France.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Nollmann
authors.affiliation: Laboratoire de Microbiologie et Génétique Moléculaires, Centre National de la Recherche Scientifique, 31062 Toulouse, France; Laboratoire de Microbiologie et Génétique Moléculaires, Université de Toulouse 3, 31062 Toulouse, France. Electronic address: jean-yves.bouet@ibcg.biotoul.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Bouet