%0 Journal Article
%T Supercoiled DNA and non-equilibrium formation of protein complexes: A quantitative model of the nucleoprotein ParBS partition complex
%+ Laboratoire Charles Coulomb (L2C)
%+ Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC )
%+ Laboratory of Pathogen Host Interactions [Montpellier] (LPHI)
%+ Laboratoire de Mécanique Générale des Milieux Continus (LMGMC)
%A Walter, Jean-Charles
%A Lepage, Thibaut
%A Dorignac, Jerome
%A Geniet, Frédéric
%A Parmeggiani, Andrea
%A Palmeri, John
%A Bouet, Jean-Yves
%A Junier, Ivan
%Z J.-C.W. was supported by a “Mode´lisation pour le Vivant’’ from MITI CNRS grant (CoilChrom). J.-Y.B. is supported by a 80 Prime CNRS grant (Numacoiled). I.J. was supported by an ATIP-Avenir grant (CNRS) and a 80 Prime CNRS grant (MIMIC). A.P. acknowledges CNRS for a dispense of a semester (demi-delegation) from teaching duties. This work wassupported in part by the LABEX NUMEV (Flagship Project Gene Expression Modeling).
%< avec comité de lecture
%@ 1553-734X
%J PLoS Computational Biology
%I Public Library of Science
%V 17
%N 4
%P e1008869
%8 2021-04-16
%D 2021
%R 10.1371/journal.pcbi.1008869
%M 33861734
%Z Life Sciences [q-bio]
%Z Physics [physics]Journal articles
%X 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.
%G English
%2 https://hal.science/hal-03438826/document
%2 https://hal.science/hal-03438826/file/Walter_Supercoiled_PCB_2021.pdf
%L hal-03438826
%U https://hal.science/hal-03438826
%~ UGA
%~ IMAG
%~ CNRS
%~ UNIV-MONTP2
%~ INPG
%~ L2C
%~ TIMC-IMAG
%~ MIPS
%~ UNIV-MONTPELLIER
%~ LPHI
%~ UNIV-LYON
%~ UGA-EPE
%~ ANR
%~ UM-2015-2021