ArticleThe Journal of biological chemistry2017
Intrinsically disordered sequences enable modulation of protein phase separation through distributed tyrosine motifs.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers.
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Who cites it
250 citing papers in PubMed, 445 citations in OpenAlex.
- Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.Bioactive materials · 2027Review
- Characterization of Liquid-Liquid Phase Separation of Companion of Cellulose Synthases under Stress Mimicking Conditions.bioRxiv : the preprint server for biology · 2026Article
- Methicillin treatment reveals that FtsZ phosphorylation influences the cell division ofPNAS nexus · 2026Article
- Molecular determinants of arginine versus lysine cation-π interactions in biomolecular condensates.Communications chemistry · 2026Article
- SARS-CoV-2 nucleocapsid protein variants have differential RNA chaperone activity.The FEBS journal · 2026Article
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- Assessing the performance of multimodal large language models in experimental information extraction from liquid-liquid phase separation literature.Scientific reports · 2026Article
- Liquid-liquid phase separation in the viral replication cycle: new paradigms and therapeutic opportunities.Archives of virology · 2026Review
- Liquid-liquid phase separation in neural development.Cellular and molecular life sciences : CMLS · 2026Review
- Antiviral activity and mechanism of purine morpholine nucleoside analogues incorporating a sulfonamide fragment.Journal of advanced research · 2026Article
- ERG phase separation attenuates cellular senescence.iScience · 2026Article
- Breaking β-sheets in FUS prion-like domain preserves phase separation and function but prevents aggregation and toxicity.bioRxiv : the preprint server for biology · 2026Article
- Key residues in SARS-CoV-2 NSP3 hypervariable region are necessary to modulate early stress granule activity.Journal of virology · 2026Article
- Molecular grammars of predicted intrinsically disordered regions that span the human proteome.Cell · 2026Article
- Diffusion-based size determination of solute particles: a method adapted for postsynaptic proteins.FEBS open bio · 2026Article
- Multiplexed Analysis of Multicomponent Biomolecular Condensates without Any Tag.Journal of the American Chemical Society · 2025Article
- Article
- Visualizing liquid-liquid phase separation and protein aggregates.Communications chemistry · 2025Review
- Key residues in SARS-CoV-2 NSP3 hyper variable region are necessary to modulate early stress granule activity.bioRxiv : the preprint server for biology · 2025Article
- Biomolecular condensate microstructure is invariant to sequence-encoded molecular and macroscopic properties.Soft matter · 2025Article
190 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Liquid-liquid phase separation (LLPS) is thought to contribute to the establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules. To understand how folded domains and IDRs can cooperate to modulate LLPS, we generated a series of engineered proteins. These were based on fusions of an IDR derived from the RNA granule protein FUS (fused in sarcoma) to a multivalent poly-Src homology 3 (SH3) domain protein that phase-separates when mixed with a poly-proline-rich-motif (polyPRM) ligand. We found that the wild-type IDR promotes LLPS of the polySH3-polyPRM system, decreasing the phase separation threshold concentration by 8-fold. Systematic mutation of tyrosine residues in Gly/Ser-Tyr-Gly/Ser motifs of the IDR reduced this effect, depending on the number but not on the position of these substitutions. Mutating all tyrosines to non-aromatic residues or phosphorylating the IDR raised the phase separation threshold above that of the unmodified polySH3-polyPRM pair. These results show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the degree of aromaticity and phosphorylation status. Our findings provide plausible mechanisms by which these sequences could alter RNA granule properties on evolutionary and cellular timescales.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.