| Autor: |
Ramachandran V; Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States., Brown W; Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States., Gayvert C; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 5011, United States., Potoyan DA; Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States.; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 5011, United States. |
| Abstrakt: |
Liquid-liquid phase separation of proteins and nucleic acids into condensate phases is a versatile mechanism for ensuring the compartmentalization of cellular biochemistry. RNA molecules play critical roles in these condensates, particularly in transcriptional regulation and stress responses, exhibiting a wide range of thermodynamic and dynamic behaviors. However, deciphering the molecular grammar that governs the stability and dynamics of protein-RNA condensates remains challenging due to the multicomponent and heterogeneous nature of condensates. In this study, we employ atomistic simulations of 20 distinct mixtures containing minimal RNA and peptide fragments which allows us to dissect the phase-separating affinities of all 20 amino acids in the presence of RNA. Our findings elucidate chemically specific interactions, hydration profiles, and ionic effects that synergistically promote or suppress protein-RNA phase separation. We map a ternary phase diagram of interactions, identifying four distinct groups of residues that promote, maintain, suppress, and disrupt protein-RNA clusters. |
