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

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,...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2023-03, Vol.13 (4), p.625
Main Authors: Dong, Weiqian, Tang, Chun, Chu, Wen-Ting, Wang, Erkang, Wang, Jin
Format: Article
Language:English
Subjects:
Amino acids
Amyotrophic lateral sclerosis
Behavior
Binding proteins
coarse-grained simulation
FUS
Health aspects
Humans
Insertion
Intrinsically Disordered Proteins - chemistry
Investigations
liquid–liquid phase separation
LLPS stability
Models, Theoretical
Molecular dynamics
molecular mass
Peptides
Phase transitions
Physiological aspects
Proteins
RNA
RNA-binding protein
RNA-Binding Proteins
Sarcoma
Simulation
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Summary: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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom13040625