Martin Erik W, Mittag Tanja
Department of Structural Biology , St. Jude Children's Research Hospital , Memphis , Tennessee 38105-3678 , United States.
Biochemistry. 2018 May 1;57(17):2478-2487. doi: 10.1021/acs.biochem.8b00008. Epub 2018 Mar 16.
Liquid-liquid phase separation seems to play critical roles in the compartmentalization of cells through the formation of biomolecular condensates. Many proteins with low-complexity regions are found in these condensates, and they can undergo phase separation in vitro in response to changes in temperature, pH, and ion concentration. Low-complexity regions are thus likely important players in mediating compartmentalization in response to stress. However, how the phase behavior is encoded in their amino acid composition and patterning is only poorly understood. We discuss here that polymer physics provides a powerful framework for our understanding of the thermodynamics of mixing and demixing and for how the phase behavior is encoded in the primary sequence. We propose to classify low-complexity regions further into subcategories based on their sequence properties and phase behavior. Ongoing research promises to improve our ability to link the primary sequence of low-complexity regions to their phase behavior as well as the emerging miscibility and material properties of the resulting biomolecular condensates, providing mechanistic insight into this fundamental biological process across length scales.
液-液相分离似乎通过形成生物分子凝聚物在细胞区室化过程中发挥关键作用。许多具有低复杂性区域的蛋白质存在于这些凝聚物中，并且它们能够在体外因温度、pH值和离子浓度的变化而发生相分离。因此，低复杂性区域可能是响应应激介导区室化的重要参与者。然而，人们对其氨基酸组成和模式如何编码相行为却知之甚少。我们在此讨论，聚合物物理学为我们理解混合和 demixing 的热力学以及相行为如何在一级序列中编码提供了一个强大的框架。我们建议根据其序列特性和相行为将低复杂性区域进一步分类为子类别。正在进行的研究有望提高我们将低复杂性区域的一级序列与其相行为以及所得生物分子凝聚物新出现的混溶性和材料特性联系起来的能力，从而在不同长度尺度上为这一基本生物学过程提供机制性见解。
