Impact of Self-Association on the Architectural Properties of Bacterial Nucleoid Proteins

Joyeux, Marc

doi:10.1016/j.bpj.2020.12.006

Cited by 9 publications

(28 citation statements)

References 69 publications

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“…In conclusion, while these experiments do not yet provide direct proof of the altered protein conformation once in the dense phase, we can speculate that this increased order persists and that it promotes protein-protein interactions that, in conjunction with the higher collision frequency in the dense phase, support formation of well-defined RNPs. The latter may proceed via preferred condensation of protein to select high-affinity recognition elements along the genomic RNA (Cubuk et al, 2021;Iserman et al, 2020), possibly in concert with M-protein interactions (Lu et al, 2021;Masters, 2019), and probably with architectural control of resulting structures being modulated by N-protein self-association properties (Joyeux, 2021).…”

Section: Discussionmentioning

confidence: 99%

Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids

Zhao

Nguyen

et al. 2021

iScience

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Nucleocapsid (N) protein of the SARS-CoV-2 virus packages the viral genome into well-defined ribonucleoprotein particles, but the molecular pathway is still unclear. N-protein is dimeric and consists of two folded domains with nucleic acid (NA) binding sites, surrounded by intrinsically disordered regions that promote liquid-liquid phase separation. Here we use biophysical tools to study N-protein interactions with oligonucleotides of different length, examining the size, composition, secondary structure, and energetics of the resulting states. We observe formation of supramolecular clusters or nuclei preceding growth into phase-separated droplets. Short hexanucleotide NA forms compact 2:2 N-protein/NA complexes with reduced disorder. Longer oligonucleotides expose additional N-protein interactions and multi-valent protein-NA interactions, which generate higher-order mixed oligomers and simultaneously promote growth of droplets. Phase separation is accompanied by a significant change in protein secondary structure, different from that caused by initial NA binding, which may contribute to the assembly of ribonucleoprotein particles within macromolecular condensates.

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Section: Discussionmentioning

confidence: 99%

Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids

Zhao

Nguyen

et al. 2021

iScience

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“…where E DNA is the internal energy of the DNA chain [Eqs. (S1)-(S7) of Joyeux (2021)], E j the internal energy of protein chain j [Eqs.…”

Section: Modelmentioning

confidence: 99%

“…-the DNA bending force constant [Eq. (S3) of Joyeux (2021)] was chosen so that the model reproduces the known persistence length of DNA under usual conditions (50 nm), -the two terminal beads of each protein chain ( m = 1 and 7) rotate freely around beads m = 2 and 6, respectively [Eq. (S10) of Joyeux (2021)], so that protein chains are significantly less rigid than the DNA chain, as is usually the case in vivo,…”

Section: Modelmentioning

confidence: 99%

“…The mechanism leading to the compaction of the DNA inside the nucleoid is a longstanding but still lively debated question (Zimmerman, 2006;de Vries, 2010;Benza et al, 2012;Joyeux, 2015Joyeux, , 2016. The three most important contributions to the compaction of the DNA are presumably (a) the cross-linking of the DNA by DNA-bridging proteins like H-NS and StpA (Spassky et al, 1984;Spurio et al, 1992;Qin et al, 2019;Joyeux, 2021), (b) DNA supercoiling, that is, the winding about itself of the circular DNA in response to the torsional stress generated by topoisomerases (Cunha et al, 2001;Stuger et al, 2002;Bates and Maxwell, 2005), and (c) the demixing of DNA and other abundant globular macromolecules which do not bind to the DNA (presumably ribosomes), resulting in a segregative phase separation (Castelnovo and Gelbart, 2004;de Vries, 2006;Krotova et al, 2010;Zinchenko et al, 2014;Joyeux, 2016Joyeux, , 2018. It is tempting to study each of these contributions separately and to rely on the hypothesis that isolated contributions "sum up" in living cells.…”

Section: Introductionmentioning

confidence: 99%

“…For example, the most abundant DNA-bridging nucleoid proteins, namely H-NS and StpA, are functional as dimers but can under certain conditions form larger oligomers (Ceschini et al, 2000;Smyth et al, 2000;Johansson et al, 2001;Badaut et al, 2002;Lim et al, 2012;Giangrossi et al, 2014;Boudreau et al, 2018). It has, moreover, been shown recently that proteins' self-association may increase dramatically their ability to shape the DNA coil (Joyeux, 2021). Therefore, the compaction of the DNA coil in mixtures of globular crowders and non-associating proteins will be compared to that of mixtures containing self-associating proteins, in order to quantify the role of proteins' self-association.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Organization of the bacterial nucleoid by DNA-bridging proteins and globular crowders

Joyeux

2023

Front. Microbiol.

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The genomic DNA of bacteria occupies only a fraction of the cell called the nucleoid, although it is not bounded by any membrane and would occupy a volume hundreds of times larger than the cell in the absence of constraints. The two most important contributions to the compaction of the DNA coil are the cross-linking of the DNA by nucleoid proteins (like H-NS and StpA) and the demixing of DNA and other abundant globular macromolecules which do not bind to the DNA (like ribosomes). The present work deals with the interplay of DNA-bridging proteins and globular macromolecular crowders, with the goal of determining the extent to which they collaborate in organizing the nucleoid. In order to answer this question, a coarse-grained model was developed and its properties were investigated through Brownian dynamics simulations. These simulations reveal that the radius of gyration of the DNA coil decreases linearly with the effective volume ratio of globular crowders and the number of DNA bridges formed by nucleoid proteins in the whole range of physiological values. Moreover, simulations highlight the fact that the number of DNA bridges formed by nucleoid proteins depends crucially on their ability to self-associate (oligomerize). An explanation for this result is proposed in terms of the mean distance between DNA segments and the capacity of proteins to maintain DNA–bridging in spite of the thermal fluctuations of the DNA network. Finally, simulations indicate that non-associating proteins preserve a high mobility inside the nucleoid while contributing to its compaction, leading to a DNA/protein complex which looks like a liquid droplet. In contrast, self-associating proteins form a little deformable network which cross-links the DNA chain, with the consequence that the DNA/protein complex looks more like a gel.

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Brownian dynamics simulations of biomolecular diffusional association processes

Muñiz‐Chicharro

Votapka

Amaro

et al. 2022

WIREs Comput Mol Sci

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Brownian dynamics (BD) is a computational method to simulate molecular diffusion processes. Although the BD method has been developed over several decades and is well established, new methodological developments are improving its accuracy, widening its scope, and increasing its application. In biological applications, BD is used to investigate the diffusive behavior of molecules subject to forces due to intermolecular interactions or interactions with material surfaces. BD can be used to compute rate constants for diffusional association, generate structures of encounter complexes for molecular binding partners, and examine the transport properties of geometrically complex molecules. Often, a series of simulations is performed, for example, for different protein mutants or environmental conditions, so that the effects of the changes on diffusional properties can be estimated. While biomolecules are commonly described at atomic resolution and internal molecular motions are typically neglected, coarse‐graining and the treatment of conformational flexibility are increasingly employed. Software packages for BD simulations of biomolecules are growing in capabilities, with several new packages providing novel features that expand the range of questions that can be addressed. These advances, when used in concert with experiment or other simulation methods, such as molecular dynamics, open new opportunities for application to biochemical and biological systems. Here, we review some of the latest developments in the theory, methods, software, and applications of BD simulations to study biomolecular diffusional association processes and provide a perspective on their future use and application to outstanding challenges in biology, bioengineering, and biomedicine. This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Software > Simulation Methods

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Impact of Self-Association on the Architectural Properties of Bacterial Nucleoid Proteins

Cited by 9 publications

References 69 publications

Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids

Energetic and structural features of SARS-CoV-2 N-protein co-assemblies with nucleic acids

Organization of the bacterial nucleoid by DNA-bridging proteins and globular crowders

Brownian dynamics simulations of biomolecular diffusional association processes

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