Effects of Mass Change on Liquid–Liquid Phase Separation of the RNA-Binding Protein Fused in Sarcoma

Abstract

In recent years, many experimental and theoretical studies of protein liquid–liquid phase separation (LLPS) have shown its important role in the processes of physiology and pathology. However, there is a lack of definite information on the regulation mechanism of LLPS in vital activities. Recently, we found that the intrinsically disordered proteins with the insertion/deletion of a non-interacting peptide segment or upon isotope replacement could form droplets, and the LLPS states are different from the proteins without those. We believed that there is an opportunity to decipher the LLPS mechanism with the mass change perspective. To investigate the effect of molecular mass on LLPS, we developed a coarse-grained model with different bead masses, including mass 1.0, mass 1.1, mass 1.2, mass 1.3, and mass 1.5 in atomic units or with the insertion of a non-interacting peptide (10 aa) and performed molecular dynamic simulations. Consequently, we found that the mass increase promotes the LLPS stability, which is based on decreasing the z motion rate and increasing the density and the inter-chain interaction of droplets. This insight into LLPS by mass change paves the way for the regulation and relevant diseases on LLPS.

Per Aspera ad Chaos: Vladimir Uversky’s Odyssey through the Strange World of Intrinsically Disordered Proteins

“…Phase separation —Liquid-liquid phase separation (LLPS) represents one of the major functional areas in which IDPs are involved and has been attracting a lot of interest in the scientific community in recent years. This is also evident from the numbers of contributions on this topic received in our SI, with five scientific articles and three reviews [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ] regarding both computational prediction and biochemical analysis of condensation propensity.…”