Supercoiled DNA and non-equilibrium formation of protein complexes: A quantitative model of the nucleoprotein ParBS partition complex - Laboratoire Charles Coulomb (L2C) Accéder directement au contenu
Article Dans Une Revue PLoS Computational Biology Année : 2021

Supercoiled DNA and non-equilibrium formation of protein complexes: A quantitative model of the nucleoprotein ParBS partition complex

Résumé

ParAB S , the most widespread bacterial DNA segregation system, is composed of a centromeric sequence, parS , and two proteins, the ParA ATPase and the ParB DNA binding proteins. Hundreds of ParB proteins assemble dynamically to form nucleoprotein parS -anchored complexes that serve as substrates for ParA molecules to catalyze positioning and segregation events. The exact nature of this ParB S complex has remained elusive, what we address here by revisiting the Stochastic Binding model (SBM) introduced to explain the non-specific binding profile of ParB in the vicinity of parS . In the SBM, DNA loops stochastically bring loci inside a sharp cluster of ParB. However, previous SBM versions did not include the negative supercoiling of bacterial DNA, leading to use unphysically small DNA persistences to explain the ParB binding profiles. In addition, recent super-resolution microscopy experiments have revealed a ParB cluster that is significantly smaller than previous estimations and suggest that it results from a liquid-liquid like phase separation. Here, by simulating the folding of long (≥ 30 kb) supercoiled DNA molecules calibrated with realistic DNA parameters and by considering different possibilities for the physics of the ParB cluster assembly, we show that the SBM can quantitatively explain the ChIP-seq ParB binding profiles without any fitting parameter, aside from the supercoiling density of DNA, which, remarkably, is in accord with independent measurements. We also predict that ParB assembly results from a non-equilibrium, stationary balance between an influx of produced proteins and an outflux of excess proteins, i.e., ParB clusters behave like liquid-like protein condensates with unconventional “leaky” boundaries.
Fichier principal
Vignette du fichier
Walter_Supercoiled_PCB_2021.pdf (2.1 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
licence : CC BY - Paternité

Dates et versions

hal-03438826 , version 1 (22-11-2021)

Licence

Paternité

Identifiants

Citer

Jean-Charles Walter, Thibaut Lepage, Jerome Dorignac, Frédéric Geniet, Andrea Parmeggiani, et al.. Supercoiled DNA and non-equilibrium formation of protein complexes: A quantitative model of the nucleoprotein ParBS partition complex. PLoS Computational Biology, 2021, 17 (4), pp.e1008869. ⟨10.1371/journal.pcbi.1008869⟩. ⟨hal-03438826⟩
365 Consultations
18 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More