Intrinsically disordered regions are poised to act as sensors of cellular chemistry

Trends in Biochemical Sciences, Год журнала: 2023, Номер 48(12), С. 1019 - 1034

Опубликована: Авг. 31, 2023

Intrinsically disordered proteins and protein regions (IDRs) are abundant in eukaryotic proteomes play a wide variety of essential roles. Instead folding into stable structure, IDRs exist an ensemble interconverting conformations whose structure is biased by sequence-dependent interactions. The absence 3D combined with high solvent accessibility, means that IDR conformational biases inherently sensitive to changes their environment. Here, we argue ideally poised act as sensors actuators cellular physicochemistry. We review the physical principles underlie sensitivity, molecular mechanisms translate this sensitivity function, recent studies where environmental sensing may key role downstream function.

Язык: Английский

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Crowder titrations enable the quantification of driving forces for macromolecular phase separation

Biophysical Journal, Год журнала: 2023, Номер 123(11), С. 1376 - 1392

Опубликована: Сен. 16, 2023

Язык: Английский

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The empty world--a view from free volume concept and the Eyring's rate process theory

Physical Chemistry Chemical Physics, Год журнала: 2024, Номер 26(41), С. 26156 - 26191

Опубликована: Янв. 1, 2024

The many-body problem is a common issue, irrespective of the scale entities under consideration.

Язык: Английский

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PEG–mCherry interactions beyond classical macromolecular crowding

Protein Science, Год журнала: 2025, Номер 34(3)

Опубликована: Фев. 19, 2025

Abstract The dense cellular environment influences bio‐macromolecular structure, dynamics, interactions, and function. Despite advancements in understanding protein–crowder predicting their precise effects on protein structure function remains challenging. Here, we elucidate the of PEG‐induced crowding fluorescent mCherry using molecular dynamics simulations fluorescence‐based experiments. We identify characterize specific structural dynamical changes mCherry. Importantly, find interactions which PEG molecules wrap around surface‐exposed residues a binding mode previously observed crystal structures. Fluorescence correlation spectroscopy experiments capture changes, including aggregation, suggesting potential role for PEG–mCherry identified simulations. Additionally, fluorescence lifetimes are influenced by not bulkier crowder dextran or another linear polymer, polyvinyl alcohol, highlighting importance crowder–protein soft interactions. This work augments our macromolecular dynamics.

Язык: Английский

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Designing salt-induced polymer-polymer biphasic systems for optimized extraction of Monascus ruber biopigments obtained by fermentation of xylose-based medium

Process Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Protein–RNA condensation kinetics via filamentous nanoclusters

Protein Science, Год журнала: 2025, Номер 34(6)

Опубликована: Май 24, 2025

Abstract Protein–RNA phase separation is at the center of membraneless biomolecular condensates governing cell physiology and pathology. Using an archetypical viral protein–RNA condensation model, we determined sequence events that starts with sub‐second formation a protomer two RNAs per protein dimer. Association additional RNA molecules to weaker secondary binding sites in this kickstarts crystallization‐like assembly molecular condensate. Primary nucleation faster than sum growth, which multistep process. nuclei grow over hundreds seconds into filaments subsequently nanoclusters approximately 600 nm diameter. Cryoelectron microscopy reveals internal structure formed by incoming layers made ribonucleoprotein oligomers, reminiscent genome packing nucleocapsid. These progress liquid condensate droplets undergo further partial coalescence yield typical hydrogel‐like coacervates may represent scaffold large factory infected cells. Our integrated experimental kinetic investigation exposes rate‐limiting steps structures along key biological pathway present across life kingdoms.

Язык: Английский

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PEG-mCherry interactions beyond classical macromolecular crowding

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 7, 2024

Abstract The dense cellular environment influences bio-macromolecular structure, dynamics, interactions and function. Despite advancements in understanding protein-crowder interactions, predicting their precise effects on protein structure function remains challenging. Here, we elucidate the of PEG-induced crowding fluorescent mCherry using molecular dynamics simulations fluorescence-based experiments. We identify characterize specific structural dynamical changes mCherry. Importantly, find which PEG molecules wrap around surface-exposed residues a binding mode previously observed crystal structures. Fluorescence correlation spectroscopy experiments capture changes, including aggregation, suggesting potential role for PEG-mCherry identified simulations. Additionally, fluorescence lifetimes are influenced by not bulkier crowder dextran or another linear polymer, polyvinyl alcohol, highlighting importance crowder-protein soft interactions. This work augments our macromolecular dynamics.

Язык: Английский

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Crowder Chain Length Variability and Excluded Volume Effect on the Phase Separation Behavior of Mucin

The Journal of Physical Chemistry Letters, Год журнала: 2024, Номер 15(42), С. 10505 - 10513

Опубликована: Окт. 11, 2024

Phase separation within cellular membranes, a critical process underpinning diverse functions, is significantly influenced by transmembrane proteins. Therefore, elucidating the behavior of protein in its phase-separated state utmost importance. Our study explores mucin milieu, aiming to determine role crowder chain length and excluded volume phase separation. Confocal microscopy images demonstrate strong partitioning into condensed hydrophobic electrostatic interactions. Fluorescence recovery after photobleaching analysis revealed increased mobility presence shorter crowders, indicating dynamic phases. Excluded calculation using theoretical model emphasizes importance under crowded conditions. findings underscore ability phase-separate conditions, highlighting crucial enhancing our understanding involvement cancer progression.

Язык: Английский

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Molecular simulations integrated with experiments for probing the interaction dynamics and binding mechanisms of intrinsically disordered proteins

Current Opinion in Structural Biology, Год журнала: 2023, Номер 84, С. 102756 - 102756

Опубликована: Дек. 19, 2023

Intrinsically disordered proteins (IDPs) exploit their plasticity to deploy a rich panoply of soft interactions and binding phenomena. Advances in tailoring molecular simulations for IDPs combined with experimental cross-validation offer an atomistic view the mechanisms that control IDP binding, function, dysfunction. The emerging theme is unbound autonomously form transient local structures self-interactions determine behavior. Recent results have shed light on whether how fold, stay or drive condensation upon binding; they achieve specificity select among competing partners. disorder-binding paradigm now being proactively used by researchers target rational drug design engineer responsive elements biosensing applications.

Язык: Английский

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Hydrodynamic and thermodynamic analysis of PEGylated human serum albumin

Biophysical Journal, Год журнала: 2024, Номер 123(16), С. 2506 - 2521

Опубликована: Июнь 18, 2024

Язык: Английский

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