Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey.
Biophys J. 2024 Jun 4;123(11):1342-1355. doi: 10.1016/j.bpj.2023.06.024. Epub 2023 Jul 5.
Multiphasic architectures are found ubiquitously in biomolecular condensates and are thought to have important implications for the organization of multiple chemical reactions within the same compartment. Many of these multiphasic condensates contain RNA in addition to proteins. Here, we investigate the importance of different interactions in multiphasic condensates comprising two different proteins and RNA using computer simulations with a residue-resolution coarse-grained model of proteins and RNA. We find that in multilayered condensates containing RNA in both phases, protein-RNA interactions dominate, with aromatic residues and arginine forming the key stabilizing interactions. The total aromatic and arginine content of the two proteins must be appreciably different for distinct phases to form, and we show that this difference increases as the system is driven toward greater multiphasicity. Using the trends observed in the different interaction energies of this system, we demonstrate that we can also construct multilayered condensates with RNA preferentially concentrated in one phase. The "rules" identified can thus enable the design of synthetic multiphasic condensates to facilitate further study of their organization and function.
多相结构在生物分子凝聚物中普遍存在，被认为对同一隔室中多种化学反应的组织具有重要意义。许多这些多相凝聚物除了蛋白质外还含有 RNA。在这里，我们使用具有蛋白质和 RNA 的残基分辨率粗粒度模型的计算机模拟，研究了由两种不同蛋白质和 RNA 组成的多相凝聚物中不同相互作用的重要性。我们发现，在含有 RNA 的双层凝聚物中，蛋白质-RNA 相互作用占主导地位，芳香族残基和精氨酸形成关键稳定相互作用。为了形成不同的相，两个蛋白质的总芳香族和精氨酸含量必须有明显的差异，我们表明，随着系统向更大的多相性驱动，这种差异会增加。利用该系统不同相互作用能的观察到的趋势，我们证明我们还可以构建具有 RNA 优先集中在一个相中的多层凝聚物。因此，可以确定“规则”来设计合成的多相凝聚物，以促进对其组织和功能的进一步研究。
