Interfacial exchange dynamics of biomolecular condensates are highly sensitive to client interactions

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 160(14)

Published: April 9, 2024

Phase separation of biomolecules can facilitate their spatiotemporally regulated self-assembly within living cells. Due to the selective yet dynamic exchange across condensate interfaces, condensates function as reactive hubs by concentrating enzymatic components for faster kinetics. The principles governing this between phases, however, are poorly understood. In work, we systematically investigate influence client–sticker interactions on dynamics protein molecules interfaces. We show that increasing affinity a model scaffold and its client causes chains dilute dense phases slow down beyond threshold interaction strength, slowdown in becomes substantial. Investigating impact symmetry, found chain also considerably slower when interact equally with different sticky residues protein. is due sequestration effect, which there fewer unbound stickers available at interface phase may attach. These findings highlight fundamental connection client–scaffold networks dynamics.

Language: Английский

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Compartmentalization of pathway sequential enzymes into synthetic protein compartments for metabolic flux optimization in Escherichia coli

Metabolic Engineering, Journal Year: 2024, Volume and Issue: 85, P. 167 - 179

Published: Aug. 18, 2024

Language: Английский

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Recent advances in engineering synthetic biomolecular condensates

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 77, P. 108452 - 108452

Published: Sept. 11, 2024

Language: Английский

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Design of a diblock-based membraneless organelle system for metabolic process control

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160239 - 160239

Published: Feb. 1, 2025

Language: Английский

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Decoding biomolecular condensate dynamics: an energy landscape approach

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(2), P. e1012826 - e1012826

Published: Feb. 10, 2025

Many eukaryotic proteins and RNAs contain low-complexity domains (LCDs) with a strong propensity for binding driving phase separation into biomolecular condensates. Mutations in LCDs frequently disrupt condensate dynamics, resulting pathological transitions to solid-like states. Understanding how the molecular sequence grammar of governs dynamics is essential uncovering their biological functions evolutionary forces that shape these sequences. To this end, we present an energy landscape framework operates on continuous ‘stickiness’ scale rather than relying explicit alphabet-based sequence. Sequences are characterized by Wasserstein distance relative thoroughly shuffled or random counterparts. Armed framework, map diagrams material dynamical properties governed key features modulated degree complexity LCD arrangements, including periodicity local disorder LCDs. Highly periodic patterns promote elasticity-dominated behavior, while sequences exhibit viscosity-dominated properties. Our results reveal minimum sticker crucial maintaining fluidity condensates, thereby avoiding glassy Moreover, demonstrate explains recent experimental findings prion predicts systematic alterations viscoelasticity. work provides unifying perspective sequence-encoded whereby landscapes conserved variable.

Language: Английский

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How the concentric organization of the nucleolus and chromatin ensures accuracy of ribosome biogenesis and drives transport

Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract The biogenetic transport of ribosomal subunit precursors must be conducted with precision to ensure production functional ribosomes. With a focus on ribosome biogenesis in higher eukaryotic cells, we here discuss the following: (1) concentric organization phases/subcompartments nucleus—including chromatin, (2) why nucleolus reorganizes when RNA synthesis is inhibited, and (3) mechanism responsible for vectorial particulate intermediates between subcompartments. We call attention evidence that nucleolar proteins can access entire volume nucleus, packaging rDNA key determinant topology, constancy contacts subcompartments, likely importance Brownian ratchet imparting both directionality quality control upon transport. Transport appears depend “self-immersion,” whereby surfaces successively interact components surrounding milieux, each which may thought as distinct solvent. result ordered process.

Language: Английский

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Selective phase separation of transcription factors is driven by orthogonal molecular grammar

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 31, 2025

Protein production is critically dependent on gene transcription rates, which are regulated by RNA polymerase and a large collection of different factors (TFs). How these selectively address genes only partially known. Recent discoveries show that the differential condensation separate TF families through phase separation may contribute to selectivity. Here we this conducting studies six TFs from three with residue-scale coarse-grained molecular dynamics simulations. Our exploration ternary diagrams reveals four dominant sticker motifs two orthogonal driving forces dictate resultant condensate morphology, pointing sequence-dependent grammar as generic mechanism drives selective transcriptional in expression. Transcription factor (TF) rates. Exploration morphology.

Language: Английский

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Multiphasic protein condensation governed by shape and valency

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115504 - 115504

Published: April 1, 2025

Language: Английский

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Differential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Biomolecular condensates form via macromolecular phase separation. Here, we report results from our characterization of synthetic formed by separation mixtures comprising two types RNA molecules and the biocompatible polymer polyethylene glycol. Purine-rich RNAs are scaffolds that drive heterotypic interactions. Conversely, pyrimidine-rich adsorbents defined weaker They adsorb onto wet interfaces coexisting phases scaffolds. Lattice-based simulations reproduce phenomenology observed in experiments these predict have different non-random orientational preferences at interfaces. Dynamics were probed using single-molecule tracking fluorogenic probes bound to molecules. These revealed dynamical anisotropy whereby motions probe parallel interface faster than perpendicular interface. Taken together, findings broad implications for designing with tunable interfacial properties.

Language: Английский

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Multiphase separation in postsynaptic density regulated by membrane geometry via interaction valency and volume

Published: May 12, 2025

Abstract Biomolecular condensates are found at various cellular locations, nucleus, cytoplasm, and membrane. These often contain multiple components can separate into phases with morphologies such as core-shell droplets, implicating functional roles. Demixing of their arrangements determined by competitive interactions locations. Recent studies reported a puzzling multiphase morphology four postsynaptic density: AMPA-receptor, NMDA-receptor, PSD-95, CaMKII. The becomes apparently reversed we move from the solubilized constructs to In this study, using system model, study behavior in solution (3D) domain formation on beneath membrane (2D) elucidate molecular mechanisms behind puzzle. Our mesoscopic simulations reproduce that CaMKII activation induces separation 3D vitro experiment AMPA-receptor/PSD-95 core NMDA-receptor/CaMKII shell. Then, obtain high valency large volume appears be major factor reversal. Interestingly, find that, while has dominant non-specific interaction system, specific multivalent overcome for membrane, reversing morphology. On layered structures receptors CaMKIIs reduce effects receptors, making dominant. is distinct condensate modulated arrangement.

Language: Английский

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