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.
J Phys Chem Lett. 2024 Oct 31;15(43):10811-10817. doi: 10.1021/acs.jpclett.4c02654. Epub 2024 Oct 21.
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.
蛋白质和核酸的液-液相分离成凝聚相是确保细胞生物化学区室化的一种通用机制。RNA 分子在这些凝聚体中起着关键作用，特别是在转录调控和应激反应中，表现出广泛的热力学和动力学行为。然而，由于凝聚体的多组分和异质性质，破译控制蛋白质-RNA 凝聚体稳定性和动力学的分子语法仍然具有挑战性。在这项研究中，我们使用包含最小 RNA 和肽片段的 20 种不同混合物的原子模拟，这使我们能够在 RNA 存在的情况下剖析所有 20 种氨基酸的相分离亲和力。我们的研究结果阐明了化学特异性相互作用、水合特性和离子效应，这些协同作用促进或抑制蛋白质-RNA 的相分离。我们绘制了一个相互作用的三元相图，确定了四个不同的残基组，它们分别促进、维持、抑制和破坏蛋白质-RNA 簇。
