ArticleProceedings of the National Academy of Sciences of the United States of America2020
Identifying sequence perturbations to an intrinsically disordered protein that determine its phase-separation behavior.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
190 citing papers in PubMed, 354 citations in OpenAlex.
- Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.Bioactive materials · 2027Review
- Designed IDPs phase separate and mix or demix according to sequence designed parameters.bioRxiv : the preprint server for biology · 2026Article
- Biomimetic Coacervate Coatings: From Phase Separation Fundamentals to Advanced Biomedical Applications.Biomimetics (Basel, Switzerland) · 2026Review
- Chain collapse, reduced dielectric, and water release drive protein phase separation.Biophysical journal · 2026Article
- Article
- Hydration free energy is an incomplete predictor of globular protein incorporation into condensates.Biophysical journal · 2026Article
- Sticker Valence Governs Chain Collapse and Liquid-Liquid Phase Separation in Peptide-Inspired Associative Polymers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dynamic and Catalytic Multiphase Coacervates.Biomacromolecules · 2026Article
- A machine learning framework for predicting and modulating condition-dependent protein phase separation.Nature communications · 2026Article
- CELF2 promotes 4R Tau splicing via nuclear clustering and drives cognitive dysfunction in tauopathy models.Nature communications · 2026Article
- A natural solution from caterpillar cuticles for flexible impact-resistant materials.Nature communications · 2026Article
- Controlling the Guanidinium Cation Rotation by Cation-π Interactions.Angewandte Chemie (International ed. in English) · 2026Article
- Analysis and design of disordered polypeptides with optimized sequence patterning properties.PLoS computational biology · 2026Article
- Interplay of Noncovalent Interactions in Phase Separation Mediated by Tyrosine-Rich and Arginine-Rich Polypeptides.Journal of the American Chemical Society · 2026Article
- Mapping interactions between disordered regions reveals promiscuity in biomolecular condensate formation.Nature communications · 2026Article
- Molecular determinants of arginine versus lysine cation-π interactions in biomolecular condensates.Communications chemistry · 2026Article
- Intrinsic Disorder as a Biomimetic Design Paradigm.Biomimetics (Basel, Switzerland) · 2026Article
- Condensate State as Determinant of Amyloid Pathology in Neurodegeneration.Biomolecules · 2026Review
- Linker histone H1 represses H3 tail acetylation induced by H4 tail acetylation and alters its dynamics.Communications biology · 2026Article
- Dilute but Dense - Reversible Crosslinking Enables Water-Rich (Bio)polymer Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Phase separation of intrinsically disordered proteins (IDPs) commonly underlies the formation of membraneless organelles, which compartmentalize molecules intracellularly in the absence of a lipid membrane. Identifying the protein sequence features responsible for IDP phase separation is critical for understanding physiological roles and pathological consequences of biomolecular condensation, as well as for harnessing phase separation for applications in bioinspired materials design. To expand our knowledge of sequence determinants of IDP phase separation, we characterized variants of the intrinsically disordered RGG domain from LAF-1, a model protein involved in phase separation and a key component of P granules. Based on a predictive coarse-grained IDP model, we identified a region of the RGG domain that has high contact probability and is highly conserved between species; deletion of this region significantly disrupts phase separation in vitro and in vivo. We determined the effects of charge patterning on phase behavior through sequence shuffling. We designed sequences with significantly increased phase separation propensity by shuffling the wild-type sequence, which contains well-mixed charged residues, to increase charge segregation. This result indicates the natural sequence is under negative selection to moderate this mode of interaction. We measured the contributions of tyrosine and arginine residues to phase separation experimentally through mutagenesis studies and computationally through direct interrogation of different modes of interaction using all-atom simulations. Finally, we show that despite these sequence perturbations, the RGG-derived condensates remain liquid-like. Together, these studies advance our fundamental understanding of key biophysical principles and sequence features important to phase separation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.