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

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

SUBMITTER: Zheng T 

PROVIDER: S-EPMC12084347 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature