NAL1 forms a molecular cage to regulate FZP phase separation

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(15)

Published: April 9, 2025

NARROW LEAF 1 ( NAL1 ), originally identified for its role in shaping leaf morphology, plant architecture, and various agronomic traits rice, has remained enigmatic terms of the molecular mechanisms governing multifaceted functions. In this study, we present a comprehensive structural analysis proteins, shedding light on how regulates phase separation physiological substrate, FRIZZY PANICLE (FZP), transcription factor. We determined that assembles as hexamer forms cage with wide central channel three narrower lateral channels, which could discriminate different substrates into catalytic sites. Most notably, our investigation unveils FZP readily condensates via both vitro vivo. fine-tunes condensation, maintaining optimal concentrations to enhance transcriptional activity. While roles include sequestration suppression or enzymatic activity, study highlights context-dependent contribution regulation. assumes pivotal regulating states these through proteolytic subsequently enhancing cascades. Our findings offer insights comprehending underpinning NAL1’s diverse functions, far-reaching implications field biology. Additionally, provide valuable guidance development rational breeding strategies aimed at crop productivity.

Language: Английский

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Phase separation in DNA repair: orchestrating the cellular response to genomic stability

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e19402 - e19402

Published: May 2, 2025

DNA repair is a hierarchically organized, spatially and temporally regulated process involving numerous factors that respond to various types of damage. Despite decades research, the mechanisms by which these are recruited depart from sites have been subject intrigue. Recent advancements in field increasingly highlighted role phase separation as critical facilitator efficiency repair. This review emphasizes how enhances concentration coordination at damage sites, optimizing efficiency. Understanding dysregulation can impair alter nuclear organization, potentially leading diseases such cancer neurodegenerative disorders, crucial. manuscript provides comprehensive understanding pivotal repair, sheds light on current suggests potential future directions for research therapeutic interventions.

Language: Английский

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A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 9, 2024

Abstract The SARS-CoV-2 nucleocapsid protein is indispensable for viral RNA genome processing. Although the N-terminal domain (NTD) suggested to mediate specific RNA-interactions, high-resolution structures with are still lacking. Available hybrid of NTD ssRNA and dsRNA provide valuable insights; however, precise mechanism complex formation remains elusive. Similarly, molecular impact mutations that have emerged since 2019 has not yet been fully explored. Using crystallography solution NMR, we investigate how influence structural integrity RNA-binding. We find both features rely on a core network residues conserved in Betacoronaviruses , crucial stability communication among flexible loop-regions facilitate RNA-recognition. Our comprehensive analysis demonstrates contacts within this guide selective RNA-interactions. propose renders evolutionarily robust plasticity its versatile processing roles.

Language: Английский

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The Nucleocapsid (N) Proteins of Different Human Coronaviruses Demonstrate a Variable Capacity to Induce the Formation of Cytoplasmic Condensates

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13162 - 13162

Published: Dec. 7, 2024

To date, seven human coronaviruses (HCoVs) have been identified. Four of these viruses typically manifest as a mild respiratory disease, whereas the remaining three can cause severe conditions that often result in death. The reasons for differences remain poorly understood, but they may be related to properties individual viral proteins. nucleocapsid (N) protein plays crucial role packaging genomic RNA and modification host cells during infection, part due its capacity form dynamic biological condensates via liquid-liquid phase separation (LLPS). In this study, we investigated N proteins derived from all HCoVs when transiently expressed cultured cells. Some transfected were observed contain cytoplasmic granules which most accumulated. Notably, SARS-CoV SARS-CoV-2 showed significantly reduced tendency condensates. condensate formation was not consequence overexpression proteins, is typical LLPS-inducing These contained components stress (SGs), indicating expression caused SGs, integrate Thus, two closely viruses, SARS-CoV-2, antagonize SG induction and/or assembly, contrast other known HCoVs.

Language: Английский

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Role of pH in Modulating RNA–Protein Interactions in TRBP2-dsRBD2: An Interplay between Conformational Dynamics and Electrostatic Interactions

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(51), P. 12698 - 12709

Published: Oct. 10, 2024

Understanding RNA–protein interactions is crucial for uncovering the mechanisms of cellular processes and can provide insights into basis various diseases, paving way development targeted therapeutic interventions. Exposure to stress conditions, such as hypoxia, leads a drop in intracellular pH, which, turn, alters ionization states amino acid residues RNA bases, affecting charge distribution electrostatic between proteins. In addition, pH also perturbs structure dynamics proteins via disruption H-bonds ionic interactions. Thus, it ascertain role modulating We have previously shown conformational interaction TAR RNA-binding protein (TRBP) double-stranded domains (dsRBD) 1 2 using solution-state NMR spectroscopy. The current study provides effect on TRBP2-dsRBD2 dsRNA. Remarkably, was observed that unit decrease an increase flexibility residues, seen experiments, addition altering surface. This led us propose dynamics-driven model where two effects flexibility, counterbalance each other. be concluded overall binding affinity governed by delicate balance its

Language: Английский

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