Evidence map›Paper›PMID 40281357›Full record

ArticleThe EMBO journal2025

Molecular insights into the effect of 1,6-hexanediol on FUS phase separation.

Tongyin Zheng, Noah Wake, Shuo-Lin Weng, Theodora Myrto Perdikari, Anastasia C Murthy, Jeetain Mittal, Nicolas L Fawzi

Abstract read
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Oligomerization of PER2 as a dynamic mode of regulation of the mammalian circadian clock.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. [Nuclear Factor I-X Regulates Molecular Pathways Related to Craniofacial Development Through Phase Separation].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Tongyin Zheng *Department of Molecular Biology, Cell Biology & Biochemistry and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, RI, USA.ORCID http://orcid.org/0000-0002-5132-6436
Noah Wake *Therapeutic Sciences Graduate Program, Brown University, Providence, RI, USA.ORCID http://orcid.org/0000-0003-4119-2574
Shuo-Lin Weng *Department of Chemistry, Texas A&M University, College Station, TX, USA.ORCID http://orcid.org/0009-0009-8082-8206
Theodora Myrto Perdikari *Center for Biomedical Engineering, Brown University, Providence, RI, USA.
Anastasia C MurthyMolecular Biology, Cell Biology & Biochemistry Graduate Program, Brown University, Providence, RI, USA.
Jeetain MittalDepartment of Chemistry, Texas A&M University, College Station, TX, USA. jeetain@tamu.edu.ORCID http://orcid.org/0000-0002-9725-6402
Nicolas L FawziDepartment of Molecular Biology, Cell Biology & Biochemistry and Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, RI, USA. nicolas_fawzi@brown.edu.ORCID http://orcid.org/0000-0001-5483-0577

Funding

TRAINING IN MOLECULAR &CELL BIOLOGY &BIOCHEMISTRYT32GM007601 · NIGMS · BROWN UNIVERSITY · PI MOWRY, KIMBERLY L. · 1985 to 2019
$6.4M
Predoctoral Training in Molecular, Cellular, and Biochemical SciencesT32GM136566 · NIGMS · BROWN UNIVERSITY · PI Mark Aikens Johnson, Erica Nicole Larschan · 2020 to 2026
$3.1M
Residue-by-residue details of FUS protein phase separation and aggregationR01GM147677 · NIGMS · BROWN UNIVERSITY · PI FAWZI, NICOLAS LUX · 2022 to 2025
$1.7M
Multiscale Computational Models to Investigate the Role of Phase Separation in BiologyR35GM153388 · NIGMS · TEXAS ENGINEERING EXPERIMENT STATION · PI Jeetain Mittal · 2024 to 2026
$1.3M
Interdisciplinary training in pharmacological sciencesT32GM139793 · NIGMS · BROWN UNIVERSITY · PI Diana M Horrigan, Sean Edward Lawler · 2021 to 2026
$1.3M
ALS Association (ALSA) 23-PDF-629Brown University (BU) Pape Adams Postdoctoral Award from the Carney InstituteHHS | NIH | National Institute of General Medical Sciences (NIGMS) R01GM147677HHS | NIH | National Institute of General Medical Sciences (NIGMS) R35GM153388HHS | NIH | National Institute of General Medical Sciences (NIGMS) T32GM007601HHS | NIH | National Institute of General Medical Sciences (NIGMS) T32GM136566HHS | NIH | National Institute of General Medical Sciences (NIGMS) T32GM139793Human Frontier Science Program (HFSP) RGP0045/2018National Science Foundation (NSF) 1644760National Science Foundation (NSF) 1845734NIGMS NIH HHS R01 GM147677NIGMS NIH HHS R35 GM153388NIGMS NIH HHS T32 GM007601NIGMS NIH HHS T32 GM136566NIGMS NIH HHS T32 GM139793
6 · The paper itself

Abstract

The alkanediol 1,6-hexanediol has been widely used to dissolve liquid-liquid phase-separated condensates in cells and in vitro, but the details of how it perturbs the molecular interactions underlying liquid-liquid assembly remain unclear. In this study we use a combination of microscopy, nuclear magnetic resonance (NMR) spectroscopy, molecular simulation, and biochemical assays to probe how alkanediols suppress phase separation and why certain isomers are more effective. We show that alkanediols of different lengths and configurations are all capable of disrupting phase separation of the RNA-binding protein Fused in Sarcoma (FUS), although potency varies depending on both geometry and hydrophobicity, which we measure directly. Alkanediols induce a shared pattern of changes to the chemical environment of the protein, to different extents depending on the specific compound. Furthermore, we use lysozyme as a model globular protein to demonstrate that alkanediols decrease the proteins' thermal stability, which is consistent with the view that they disrupt phase separation driven by hydrophobic groups. Conversely, 1,6-hexanediol does not disrupt charge-mediated phase separation, such as FUS RGG-RNA and poly-lysine/poly-aspartic acid condensates. All-atom simulations show that hydroxyl groups in alkanediols mediate interactions with the protein backbone and polar amino acid side chains, while the aliphatic chain allows contact with hydrophobic and aromatic residues, providing a molecular picture of how amphiphilic interactions disrupt FUS phase separation.

Indexed as

GlycolsRNA-Binding Protein FUSHumansHydrophobic and Hydrophilic InteractionsMagnetic Resonance SpectroscopyMolecular Dynamics SimulationMuramidasePhase SeparationFUS protein, humanGlycolsMuramidaseRNA-Binding Protein FUSHydrophobicityMolecular SimulationNMR SpectroscopyProtein FoldingRNA

Identifiers

PMID40281357
PMCPMC12084347

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Registered trials

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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.