Electrostatics of Salt-Dependent Reentrant Phase Behaviors Highlights Diverse Roles of ATP in Biomolecular Condensates DOI Open Access
Yi‐Hsuan Lin, Tae Hun Kim, Suman Das

et al.

Published: Sept. 4, 2024

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, e.g., reentrant behaviors some instances but not others. Experimental data rationalized modeling using analytical theory, molecular dynamics, polymer field-theoretic simulations, indicating general that interchain salt bridges enhance LLPS polyelectrolytes such as high valency ATP-magnesium significant factor colocalization with condensed phases, similar trends observed several other IDRs. Our findings underscore role modulating ion concentrations functional ramifications.

Language: Английский

Liquid–Liquid Phase Separation Modifies the Dynamic Properties of Intrinsically Disordered Proteins DOI Creative Commons
Serafima Guseva,

Vincent Schnapka,

Wiktor Adamski

et al.

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

58
Molecular Crowding: The History and Development of a Scientific Paradigm DOI Creative Commons
Caterina Alfano, Yann Fichou, Klaus Huber

et al.

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
Emergent microenvironments of nucleoli DOI Creative Commons
Matthew R. King, Kiersten M. Ruff, Rohit V. Pappu

et al.

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
Single-fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates DOI Creative Commons
Tingting Wu, Matthew R. King, Yuanxin Qiu

et al.

Nature Physics, Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Language: Английский

Citations

3
Peptide-Mediated Liquid-Liquid Phase Separation and Biomolecular Condensates DOI

Guangle Li,

Chengqian Yuan, Xuehai Yan

et al.

Soft Matter, Journal Year: 2025, Volume and Issue: 21(10), P. 1781 - 1812

Published: Jan. 1, 2025

Peptide-mediated liquid–liquid phase separation (LLPS) underpins the formation of dynamic biomolecular condensates, regulated by diverse molecular interactions, and highlights potential applications in drug delivery synthetic biology.

Language: Английский

Citations

2
Electrostatics of salt-dependent reentrant phase behaviors highlights diverse roles of ATP in biomolecular condensates DOI Creative Commons
Yi‐Hsuan Lin, Tae Hun Kim, Suman Das

et al.

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

2
Binary peptide coacervates as an active model for biomolecular condensates DOI Creative Commons
Shoupeng Cao, Peng Zhou, Guizhi Shen

et al.

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

2
Biological importance of arginine: A comprehensive review of the roles in structure, disorder, and functionality of peptides and proteins DOI
Munishwar N. Gupta, Vladimir N. Uversky

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 257, P. 128646 - 128646

Published: Dec. 6, 2023

Language: Английский

Citations

33
Cross-Talk of Cation−π Interactions with Electrostatic and Aromatic Interactions: A Salt-Dependent Trade-off in Biomolecular Condensates DOI Creative Commons

Milan Kumar Hazra,

Yaakov Levy

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

26
Aromatic Residues in Proteins: Re-Evaluating the Geometry and Energetics of π–π, Cation−π, and CH−π Interactions DOI Creative Commons

Rivka Calinsky,

Yaakov Levy

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(36), P. 8687 - 8700

Published: Sept. 2, 2024

Aromatic residues can participate in various biomolecular interactions, such as π-π, cation-π, and CH-π which are essential for protein structure function. Here, we re-evaluate the geometry energetics of these interactions using quantum mechanical (QM) calculations, focusing on pairwise involving aromatic amino acids Phe, Tyr, Trp cationic Arg Lys. Our findings reveal that π-π while energetically favorable, less abundant structured proteins than commonly assumed often overshadowed by previously underappreciated, yet prevalent, interactions. Cation-π particularly those Arg, show strong binding energies a specific geometric preference toward stacked conformations, despite global QM minimum, suggesting rather perpendicular T-shape conformation should be more favorable. results support nuanced understanding stabilization via residues. On one hand, our challenge traditional emphasis showing cation-π contribute significantly to their structure. other appear key stabilizers solvated regions thus may important intrinsically disordered proteins.

Language: Английский

Citations

9