Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108188 - 108188
Published: Jan. 1, 2025
Language: Английский
Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(19), P. 10548 - 10563
Published: May 5, 2023
Liquid–liquid phase separation of flexible biomolecules has been identified as a ubiquitous phenomenon underlying the formation membraneless organelles that harbor multitude essential cellular processes. We use nuclear magnetic resonance (NMR) spectroscopy to compare dynamic properties an intrinsically disordered protein (measles virus NTAIL) in dilute and dense phases at atomic resolution. By measuring 15N NMR relaxation different field strengths, we are able characterize dynamics crowded conditions amplitude timescale motional modes those present organelle. Although local backbone conformational sampling appears be largely retained, occurring on all detectable timescales, including librational, dihedral angle segmental, chainlike motions, considerably slowed down. Their relative amplitudes also drastically modified, with slower, chain-like motions dominating profile. In order provide additional mechanistic insight, performed extensive molecular simulations under self-crowding concentrations comparable found liquid phase. Simulation broadly reproduces impact condensed both free energy landscape kinetic interconversion between states. particular, experimentally observed reduction fastest component correlates higher levels intermolecular contacts or entanglement simulations, reducing space available this mode strongly conditions.
Language: Английский
Citations
56
Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(6), P. 3186 - 3219
Published: March 11, 2024
It is now generally accepted that macromolecules do not act in isolation but "live" a crowded environment, is, an environment populated by numerous different molecules. The field of molecular crowding has its origins the far 80s became only end 90s. In present issue, we discuss various aspects are influenced and need to consider effects. This Review meant as introduction theme analysis evolution concept through time from colloidal polymer physics more biological perspective. We introduce themes will be thoroughly treated other Reviews issue. our intentions, each may stand itself, complete collection aspiration provide complementary perspectives propose holistic view crowding.
Language: Английский
Citations
37
Nucleus, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 5, 2024
In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The prominent coexisting are fibrillar center (FC), dense component (DFC), and granular (GC). Here, we review recent efforts in profiling sub-phase compositions shed light on types of physicochemical properties emerge from compositional biases territorial organization specific macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features substrate binding domains, intrinsically disordered regions, multivalence these distinct domains / regions. introduce concept a barcode emergent nucleoli. Although our knowledge full remains incomplete, hope prompts investigations into undiscovered engenders an appreciation for how why unique microenvironments control biochemical reactions
Language: Английский
Citations
22
Nature Physics, Journal Year: 2025, Volume and Issue: unknown
Published: March 14, 2025
Language: Английский
Citations
3
International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 257, P. 128646 - 128646
Published: Dec. 6, 2023
Language: Английский
Citations
33
The Journal of Physical Chemistry Letters, Journal Year: 2023, Volume and Issue: 14(38), P. 8460 - 8469
Published: Sept. 18, 2023
Biomolecular condensates are essential for cellular functionality, yet the complex interplay among diverse molecular interactions that mediate their formation remains poorly understood. Here, using coarse-grained dynamics simulations, we address contribution of cation-π to stability formed via liquid-liquid phase separation. We found greater stabilization up 80% in from peptides with higher aromatic residue content or less charge clustering. The droplet increases increasing ionic strength, suggesting a trade-off between and electrostatic interactions. Cation-π interactions, therefore, can compensate reduced such as occurs at salt concentrations sequences charged Designing desired biophysical characteristics therefore requires quantification not only individual but also cross-talks involving charge-charge, π-π,
Language: Английский
Citations
25
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 11, 2025
Abstract Liquid-liquid phase separation of biomolecules is crucial for maintaining the functional organization in biological systems. Intrinsically disordered proteins are particularly prone to form phase-separated condensates response various physicochemical triggers. While effect ionic strength and temperature on dynamics have been studied extensively, influence pH less explored. Here, we study a model glycine-rich protein present tick bioadhesive, given its capability undergo separation. After confirming nature through spectroscopy, investigated dependence underlying molecular mechanisms. Our findings reveal that significantly influences hydrophobicity via residues, driving notable variations coacervation behavior (propensity, progression) shaping material properties (viscosity, interfacial activity) formed condensates. Given ubiquitous presence biology, this provides valuable insights about broad implications pH-dependent intrinsically proteins.
Language: Английский
Citations
1
eLife, Journal Year: 2025, Volume and Issue: 13
Published: March 3, 2025
Liquid-liquid phase separation (LLPS) involving intrinsically disordered protein regions (IDRs) is a major physical mechanism for biological membraneless compartmentalization. The multifaceted electrostatic effects in these biomolecular condensates are exemplified here by experimental and theoretical investigations of the different salt- ATP-dependent LLPSs an IDR messenger RNA-regulating Caprin1 its phosphorylated variant pY-Caprin1, exhibiting, example, reentrant behaviors some instances but not others. Experimental data rationalized modeling using analytical theory, molecular dynamics, polymer field-theoretic simulations, indicating that interchain ion bridges enhance LLPS polyelectrolytes such as high valency ATP-magnesium significant factor colocalization with condensed phases, similar trends observed other IDRs. nature features complements ATP’s involvement π-related interactions amphiphilic hydrotrope, underscoring general role modulating concentrations functional ramifications.
Language: Английский
Citations
1
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 11, 2025
Abstract Biomolecular condensates formed by proteins and nucleic acids are critical for cellular processes. Macromolecule-based coacervate droplets liquid-liquid phase separation serve as synthetic analogues, but limited complex compositions high molecular weights. Recently, short peptides have emerged an alternative component of coacervates, tend to form metastable microdroplets that evolve into rigid nanostructures. Here we present programmable coacervates using binary mixtures diphenylalanine-based peptides. We show the presence different stabilizes prevents formation structures, allowing peptide be used stable adaptive compartments. This approach allows fine control droplet dynamic morphological changes in response physiological triggers. As compartments, sequester hydrophobic molecules enhance bio-orthogonal catalysis. In addition, incorporation model cells enables design Boolean logic gates. Our findings highlight potential creating biomimetic systems provide insight principles biomolecular condensates.
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Jan. 27, 2023
Abstract Biomolecular condensates are viscoelastic materials. Simulations predict that fluid-like condensations defined by spatially inhomogeneous organization of the underlying molecules. Here, we test these predictions using single-fluorogen tracking and super-resolution imaging. Specifically, leverage localization orientational preferences freely diffusing fluorogens solvatochromic effect whereby specific turned on in response to condensate microenvironments. We deployed three different probe microenvironments molecular protein-based condensates. The spatiotemporal resolution environmental sensitivity afforded imaging shows internal environments more hydrophobic than coexisting dilute phases. Molecules within organized a manner, this gives rise slow-moving nanoscale clusters coexist with fast-moving Fluorogens localize preferentially interface help us map their distinct features. Our findings provide structural dynamical basis for viscoelasticity
Language: Английский
Citations
22