Rational design of phytovirucide inhibiting nucleocapsid protein aggregation in tomato spotted wilt virus

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

Published: Feb. 27, 2025

Ineffectiveness of managing plant viruses by chemicals has posed serious challenges in crop production. Recently, phase separation shown to play a key role viral lifecycle. Using inhibitors that can disturb biomolecular condensates formed for virus control been reported medical field. However, the applicability this promising antiviral tactic protection not explored. Here, we report an inhibitor, Z9, targets tomato spotted wilt (TSWV) N protein. Z9 is capable interacting with amino acids nucleic acid binding region TSWV N, disrupting assembly and RNA into phase-separated condensates, reduction which detrimental stability This study provides strategy separation-based control. Biomolecular have recognized as crucial process life cycle. authors inhibitor targeting nucleocapsid protein (N) disrupt its potential

Language: Английский

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Native Mass Spectrometry Captures the Conformational Plasticity of Proteins with Low-Complexity Domains

JACS Au, Journal Year: 2025, Volume and Issue: 5(1), P. 281 - 290

Published: Jan. 8, 2025

Disordered regions are an important functional feature of many multidomain proteins. A prime example is proteins in membraneless organelles, which contain folded domains that engage specific interactions and disordered low-complexity (LC) mediate liquid-liquid phase separation. Studying these complex architectures remains challenging due to their conformational variability. Native mass spectrometry (nMS) routinely employed analyze conformations or proteins; however, its ability with LC has not been investigated. Here, we the ionization states designed model recapitulate key features found organelles. Our results show charge state distributions (CSDs) nMS reflect partial disorder regardless protein sequence, providing insights into plasticity interactions. By applying same CSD analysis a spider silk fragment, find between trigger assembly simultaneously induce changes domains. Lastly, using intact nucleosomes, demonstrate CSDs good predictor for content native assemblies. We conclude reliably informs about landscape domains, crucial understanding condensates cellular environments.

Language: Английский

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Light-induced programmable solid–liquid phase transition of biomolecular condensates for improved biosynthesis

Trends in biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Thermal cycling resets the irreversible liquid-to-solid transition of peptide condensates during aging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

ABSTRACT The ability of biomolecular condensates to reversibly dissolve and reform is crucial for maintaining cellular stability functions. In metabolically active cells, stress granules can rapidly assemble disassemble in response environmental changes. However, as metabolic rates decline with aging, persist longer, disrupting mRNA translation responses. Temperature, a physical stimulus, plays key role controlling condensate formation, dissolution, material properties. this study, we explore how the reversibility liquid-to-solid transition be modulated by temperature change. Our findings reveal that aged exhibit reduced responsiveness external stimuli. By using thermal cycling experiments simulate repeated heat stress, found time taken irreversible fiber formation could delayed up 4.7-fold compared without cycles. We also dissolution rate progressively slows they age but remain more stable Importantly, our results indicate continuous cycles liquid-liquid phase separation act reset mechanism, preserving from further transition. These provide valuable insights into aging impacts behavior highlight potential strategies preserve function through controlled transitions.

Language: Английский

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Liquid-liquid crystalline phase separation of spider silk proteins

Communications Chemistry, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 12, 2024

Liquid-liquid phase separation (LLPS) of proteins can be considered an intermediate solubility regime between disperse solutions and solid fibers. While LLPS has been described for several pathogenic amyloids, recent evidence suggests that it is similarly relevant functional amyloids. Here, we review the links spider silk (spidroins) its role in spinning process. Major ampullate spidroins undergo mediated by stickers spacers their repeat regions. During spinning, droplets shift from liquid to crystalline states. Shear force, altered ion composition, pH changes cause micelle-like spidroin assemblies form increasingly ordered liquid-crystalline phase. Interactions polyalanine regions ultimately yield characteristic β-crystalline structure mature dragline Based on these findings, hypothesize liquid-liquid (LLCPS) describe molecular macroscopic features transitions major during speculate whether other types may use a similar mechanism convert dope fiber.

Language: Английский

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Metastable Liquid–Liquid Phase Separation and Aging Lead to Strong Processing Path Dependence in Mini‐Spidroin Solutions

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Abstract Recombinant silk proteins provide a route toward sustainable and biocompatible materials. For making such materials, the assembly process from dilute protein into functional material is central. The mechanism in engineered materials by necessity different natural ones—this poses challenges but also opens opportunities for scaling up developing novel properties. phase behavior of mini‐spidroin, NT‐2Rep‐CT studied, which widely studied variant recombinant silk. can be triggered to assemble lowering pH, even at high pH—considered as storage conditions—it various states, forming condensates, clusters, gels, soluble protein. It shown how its phases evolve through both metastable dynamically arrested states. observed solutions highly complex, elements thereof diagrams associated with polymers, colloidal systems, globular are found. Based on characterization cluster formation structural intermediates, minimalist diagram proposed argues that understanding insight via behavior, especially central designing their processing applications.

Language: Английский

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Engineering microbial cell factories by multiplexed spatiotemporal control of cellular metabolism: Advances, challenges, and future perspectives

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 79, P. 108497 - 108497

Published: Dec. 5, 2024

Language: Английский

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Recombinant silk protein condensates show widely different properties depending on sample background

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(46), P. 11953 - 11967

Published: Jan. 1, 2024

Background molecules such as DNA affect the formation and properties of recombinant spider silk protein condensates.

Language: Английский

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