Year: 2024
Type: article
Abstract: Phase transitions are important to understand cell dynamics, and the maturation of liquid droplets is relevant to neurodegenerative disorders. We combined NMR and Raman spectroscopies with microscopy to follow, over a period of days to months, droplet maturation of the protein fused in sarcoma (FUS). Our study reveals that the surface of the droplets plays a critical role in this process, while RNA binding prevents it. The maturation kinetics are faster in an agarose-stabilized biphasic sample compared with a monophasic condensed sample, owing to the larger surface-to-volume ratio. In addition, Raman spectroscopy reports structural differences upon maturation between the inside and the surface of droplets, which is comprised of β-sheet content, as revealed by solid-state NMR. In agreement with these observations, a solid crust-like shell is observed at the surface using microaspiration. Ultimately, matured droplets were converted into fibrils involving the prion-like domain as well as the first RGG motif.
Source: Nature Chemical Biology
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
Awards: G1278951854, G2095338500, G2222446239, SFB 1551: Polymerkonzepte zum Verstehen zellulärer Funktionen, Zelluläre Organisation durch Phasenseparationsprozesse untersucht mittels FestkörperNMR: Erkenntnise von RNAbindenden Proteinen und konstruierten Spinnenseideproteinen, G4376339242, ProteinNukleinsäureErkennung untersucht durch FestkörperKernresonanzspektroskopie bei schnellen Rotationen um den magischen Winkel, Role of Disordered Regions in RNA-Binding Proteins for Function and Pathology, G7979452392
OpenAlex ID: W4392646903