Liquid–Liquid Phase Separation of the Intrinsically Disordered Domain of the Fused in Sarcoma Protein Results in Substantial Slowing of Hydration Dynamics

• Published in: The journal of physical chemistry letters Vol. 14; no. 49; pp. 11224 - 11234
• Main Authors: Krevert, Carola S., Chavez, Daniel, Chatterjee, Sayantan, Stelzl, Lukas S., Pütz, Sabine, Roeters, Steven J., Rudzinski, Joseph F., Fawzi, Nicolas L., Girard, Martin, Parekh, Sapun H., Hunger, Johannes
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14.12.2023
• Subjects: Amides; Humans; Hydrogen; Letter; Physical Insights into Materials and Molecular Properties; Proteins; Sarcoma
• ISSN: 1948-7185; 1948-7185
• DOI: 10.1021/acs.jpclett.3c02790

Formation of liquid condensates plays a critical role in biology via localization of different components or via altered hydrodynamic transport, yet the hydrogen-bonding environment within condensates, pivotal for solvation, has remained elusive. We explore the hydrogen-bond dynamics within condensates formed by the low-complexity domain of the fused in sarcoma protein. Probing the hydrogen-bond dynamics sensed by condensate proteins using two-dimensional infrared spectroscopy of the protein amide I vibrations, we find that frequency–frequency correlations of the amide I vibration decay on a picosecond time scale. Interestingly, these dynamics are markedly slower for proteins in the condensate than in a homogeneous protein solution, indicative of different hydration dynamics. All-atom molecular dynamics simulations confirm that lifetimes of hydrogen-bonds between water and the protein are longer in the condensates than in the protein in solution. Altered hydrogen-bonding dynamics may contribute to unique solvation and reaction dynamics in such condensates.