Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Key Laboratory for Neuroscience, Ministry of Education/National Health Commission of China, Peking University, Beijing, China.
Am J Physiol Cell Physiol. 2023 Feb 1;324(2):C236-C246. doi: 10.1152/ajpcell.00280.2022. Epub 2022 Dec 12.
Life consists of numberless functional biomolecules that exist in various states. Besides well-dissolved phases, biomolecules especially proteins and nucleic acids can form liquid droplets through liquid-liquid phase separation (LLPS). Stronger interactions promote a solid-like state of biomolecular condensates, which are also formerly referred to as detergent-insoluble aggregates. Solid-like condensates exist in vivo physiologically and pathologically, and their formation has not been fully understood. Recently, more and more research has proven that liquid to solid phase transition (LST) is an essential way to form solid condensates. In this review, we summarized the regions in the sequence that have different impacts on phase transition and emphasized that the LST is affected by its sequence characteristics. Moreover, increasing evidence unveiled that LST is affected by various solution conditions. We discussed solution conditions like protein concentration, pH, ATP, ions, and small molecules in a solution. Methods have been established to study these solid phase components. Here, we summarized low-throughput experimental techniques and high-throughput omics methods in the study of the LST.
生命由无数种存在于不同状态的功能生物分子组成。除了良好溶解的相态外，生物分子，特别是蛋白质和核酸，可以通过液-液相分离（LLPS）形成液滴。较强的相互作用促进生物分子凝聚物形成类似固体的状态，这些凝聚物也以前被称为去污剂不溶性聚集体。类似固体的凝聚物在体内存在于生理和病理状态下，其形成尚未完全理解。最近，越来越多的研究证明，从液相到固相的转变（LST）是形成固相凝聚物的一种重要方式。在这篇综述中，我们总结了序列中对相变有不同影响的区域，并强调了 LST 受到其序列特征的影响。此外，越来越多的证据揭示了 LST 受到各种溶液条件的影响。我们讨论了溶液中的蛋白质浓度、pH 值、ATP、离子和小分子等条件。已经建立了研究这些固相成分的方法。在这里，我们总结了 LST 研究中低通量实验技术和高通量组学方法。
