ArticleCell2018
A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,165 papers.
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1,165 citing papers in PubMed, 2,160 citations in OpenAlex.
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- Programmable DNA protonuclei reveal environmental context on protein phase separation.Nature communications · 2026Article
- The thermodynamic state map of biomolecular condensates.Communications biology · 2026Review
- Electrostatic-Hydrophobic Competition Induces Re-Entrant Phase Separation in Designer Polypeptides.ACS omega · 2026Article
- Interpretable biophysical neural networks of transcriptional activation domains separate roles of protein abundance and coactivator binding.Cell systems · 2026Article
- Liquid-Liquid Phase Separation-Enhanced Multienzyme Catalysis: Mechanisms and Applications.ChemSusChem · 2026Review
- Mapping high resolution, multidimensional phase diagrams of near-physiological protein condensates.Nature communications · 2026Article
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- Chain collapse, reduced dielectric, and water release drive protein phase separation.Biophysical journal · 2026Article
- Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins.Biochemistry and biophysics reports · 2026Review
- hnRNPK condensates facilitate enhancer-promoter looping and RNA polymerase II recruitment.Nature genetics · 2026Article
- Advances in engineering and applications of synthetic phase-separated membraneless organelles in biotechnology.Synthetic and systems biotechnology · 2026Review
- Article
1,105 more citing papers are in PubMed but not listed here.
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14 authors at 3 institutions in 3 countries.
Funding
Abstract
Proteins such as FUS phase separate to form liquid-like condensates that can harden into less dynamic structures. However, how these properties emerge from the collective interactions of many amino acids remains largely unknown. Here, we use extensive mutagenesis to identify a sequence-encoded molecular grammar underlying the driving forces of phase separation of proteins in the FUS family and test aspects of this grammar in cells. Phase separation is primarily governed by multivalent interactions among tyrosine residues from prion-like domains and arginine residues from RNA-binding domains, which are modulated by negatively charged residues. Glycine residues enhance the fluidity, whereas glutamine and serine residues promote hardening. We develop a model to show that the measured saturation concentrations of phase separation are inversely proportional to the product of the numbers of arginine and tyrosine residues. These results suggest it is possible to predict phase-separation properties based on amino acid sequences.
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