Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(4), P. 1899 - 1949

Published: Feb. 8, 2024

Macromolecular crowding affects the activity of proteins and functional macromolecular complexes in all cells, including bacteria. Crowding, together with physicochemical parameters such as pH, ionic strength, energy status, influences structure cytoplasm thereby indirectly function. Notably, also promotes formation biomolecular condensates by phase separation, initially identified eukaryotic cells but more recently discovered to play key functions Bacterial require a variety mechanisms maintain homeostasis, particular environments fluctuating conditions, is emerging one mechanism. In this work, we connect homeostasis function bacterial cell compare supramolecular structures found bacteria those cells. We focus on effects separation control chromosome replication, segregation, division, discuss contribution fitness adaptation environmental stress.

Language: Английский

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Fundamental Aspects of Phase-Separated Biomolecular Condensates

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(13), P. 8550 - 8595

Published: June 17, 2024

Biomolecular condensates, formed through phase separation, are upending our understanding in much of molecular, cell, and developmental biology. There is an urgent need to elucidate the physicochemical foundations behaviors properties biomolecular condensates. Here we aim fill this by writing a comprehensive, critical, accessible review on fundamental aspects phase-separated We introduce relevant theoretical background, present basis for computation experimental measurement condensate properties, give mechanistic interpretations terms interactions at molecular residue levels.

Language: Английский

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Bacterial chromatin proteins, transcription, and DNA topology: Inseparable partners in the control of gene expression

Molecular Microbiology, Journal Year: 2024, Volume and Issue: 122(1), P. 81 - 112

Published: June 7, 2024

Abstract DNA in bacterial chromosomes is organized into higher‐order structures by DNA‐binding proteins called nucleoid‐associated (NAPs) or chromatin (BCPs). BCPs often bind to near loci transcribed RNA polymerase (RNAP) and can either increase decrease gene expression. To understand the mechanisms which alter transcription, one must consider both steric effects topological forces that arise when deviates from its fully relaxed double‐helical structure. Transcribing RNAP creates negative (−) supercoils upstream positive (+) downstream whenever are unable rotate freely. This supercoiling generates resist forward translocation of through unless constrained relieved topoisomerases. also may enhance stress overall inhibit aid transcription. Here, we review current understanding how RNAP, BCPs, topology interplay control

Language: Английский

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Bacterial nucleoid is a riddle wrapped in a mystery inside an enigma

Journal of Bacteriology, Journal Year: 2024, Volume and Issue: 206(3)

Published: Feb. 15, 2024

Bacterial chromosome, the nucleoid, is traditionally modeled as a rosette of DNA mega-loops, organized around proteinaceous central scaffold by nucleoid-associated proteins (NAPs), and mixed with cytoplasm transcription translation. Electron microscopy fixed cells confirms dispersal cloud-like nucleoid within ribosome-filled cytoplasm. Here, I discuss evidence that in live forms phase separate from riboprotein phase, "riboid." argue nucleoid-riboid interphase, where interacts NAPs, transcribing RNA polymerases, nascent transcripts, ssRNA chaperones, zone. An active part separation, zone enforces segregation centrally positioned information (the nucleoid) surrounding action riboid), translation happens, protein accumulates, metabolism occurs. speculate HU NAP mostly tiles up periphery-facilitating mobility but also supporting interphase. Besides extruding plectonemically supercoiled condensins could compact them into solenoids uniform rings, while support rigidity rotation these rings. The two-phase arrangement allows bacterial cell to organize dogma activities, (from center its periphery) replicates segregates, transcribed, mRNA handed over ribosomes, translated proteins, finally, used recycled nucleotides at inner membrane. resulting information-action conveyor, one activity naturally leading next one, explains efficiency prokaryotic design-even though main intracellular transportation mode free diffusion.

Language: Английский

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Polyphosphate: The “Dark Matter” of Bacterial Chromatin Structure

Molecular Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

ABSTRACT Polyphosphate (polyP), broadly defined, consists of a chain orthophosphate units connected by phosphoanhydride bonds. PolyP is the only universal inorganic biopolymer known to date and present in all three domains life. At first approximation polyP appears be simple, featureless, flexible polyanion. A growing body evidence suggests that not as featureless originally thought: it can form wide variety complexes condensates through association with proteins, nucleic acids, ions. It becoming apparent emergent properties condensate superstructures forms are both complex dynamic. Importantly, affect bacterial chromatin, directly mediating interactions between DNA proteins. In an increasing number contexts, profoundly impacts chromosomal structure gene regulation bacteria, thus serving rarely considered, but highly important, component nucleoid biology.

Language: Английский

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Biomolecular condensates as stress sensors and modulators of bacterial signaling

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012413 - e1012413

Published: Aug. 15, 2024

Microbes exhibit remarkable adaptability to environmental fluctuations. Signaling mechanisms, such as two-component systems and secondary messengers, have long been recognized critical for sensing responding cues. However, recent research has illuminated the potential of a physical adaptation mechanism in signaling—phase separation, which may represent ubiquitous compartmentalizing biochemistry within cytoplasm context bacteria that frequently lack membrane-bound organelles. This review considers broader prospect phase separation play roles rapid stress response mechanisms pathogens. It is well established weak multivalent interactions between disordered regions, coiled-coils, other structured domains can form condensates via be regulated by specific parameters some cases. The process itself acts responsive sensor, influenced changes protein concentration, posttranslational modifications, temperature, salts, pH, oxidative stresses. environmentally triggered can, turn, regulate functions recruited biomolecules, providing stressful conditions. As examples, we describe biochemical pathways organized are essential cell physiology signaling features. These include proteins organize modify chromosome (Dps, Hu, SSB), decay, modification RNA (RNase E, Hfq, Rho, polymerase), those involved signal transduction (PopZ, PodJ, SpmX) (aggresomes polyphosphate granules). We also summarize pathogens function challenges targeting biomolecular next-generation antimicrobial therapeutics. Together, this illuminates emerging significance microbial signaling, responses, regulation provides framework microbiologists consider diverse

Language: Английский

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Rok from B. subtilis: Bridging genome structure and transcription regulation

Molecular Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: March 21, 2024

Abstract Bacterial genomes are folded and organized into compact yet dynamic structures, called nucleoids. Nucleoid orchestration involves many factors at multiple length scales, such as nucleoid‐associated proteins liquid–liquid phase separation, has to be compatible with replication transcription. Possibly, genome organization plays an intrinsic role in transcription regulation, addition classical factors. In this review, we provide arguments supporting view using the Gram‐positive bacterium Bacillus subtilis a model. Proteins BsSMC, HBsu Rok all impact structure of B. chromosome. Particularly for Rok, there is compelling evidence that it combines its structural function global gene regulator. Many studies describe either but rarely both addressed same time. Here, review sides coin integrate them one forms unusually stable DNA–DNA bridges ability likely underlies repressive effect on by preventing RNA polymerase from binding DNA or trapping inside loops. Partner needed change relieve Rok‐mediated repression. Lastly, investigate which features characterize H‐NS‐like proteins, family that, present, lacks clear definition.

Language: Английский

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Physical models of bacterial chromosomes

Molecular Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract The interplay between bacterial chromosome organization and functions such as transcription replication can be studied in increasing detail using novel experimental techniques. Interpreting the resulting quantitative data, however, theoretically challenging. In this minireview, we discuss how connecting observations to biophysical theory modeling give rise new insights on organization. We consider three flavors of models complexity: simple polymer that explore physical constraints, confinement or plectoneme branching, affect organization; bottom‐up mechanistic connect these constraints their underlying causes, for instance, compaction macromolecular crowding, supercoiling transcription; finally, data‐driven methods inferring interpretable directly from complex data. Using recent examples, both deepen our understanding chromosomes are structured predictions about

Language: Английский

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Live to fight another day: The bacterial nucleoid under stress

Molecular Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

The bacterial chromosome is both highly supercoiled and bound by an ensemble of proteins RNA, causing the DNA to form a compact structure termed nucleoid. nucleoid serves condense, protect, control access through variety mechanisms that remain incompletely understood. also dynamic structure, able change in size composition. nature particularly apparent when studying effects various stresses on bacteria, which require cells protect their alter patterns transcription. Stresses can lead large changes organization composition timescales as short few minutes. Here, we summarize some recent advances our understanding how stress chromosomes.

Language: Английский

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Reentrant DNA shells tune polyphosphate condensate size

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 26, 2024

The inorganic biopolymer polyphosphate (polyP) occurs in all domains of life and affects myriad cellular processes. A longstanding observation is polyP's frequent proximity to chromatin, and, many bacteria, its occurrence as magnesium (Mg2+)-enriched condensates embedded the nucleoid region, particularly response stress. physical basis interaction between polyP, DNA Mg2+, resulting effects on organization polyP condensates, remain poorly understood. Here, using a minimal system DNA, we find that can form shells around polyP-Mg2+ condensates. These show reentrant behavior, is, they within window Mg2+ concentrations, representing tunable architecture with potential relevance other multicomponent This surface association tunes condensate size morphology manner dependent length concentration, even at concentrations orders magnitude lower than found cell. Our work also highlights remarkable capacity two primordial species organize DNA. Polyphosphate processes often near authors forms vitro, controlling properties.

Language: Английский

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