NSF Research Triangle Materials Research Science and Engineering Center, Duke University, Durham, North Carolina 27708, USA.
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
Nat Chem. 2017 Jun;9(6):509-515. doi: 10.1038/nchem.2715. Epub 2017 Jan 30.
Dynamic protein-rich intracellular structures that contain phase-separated intrinsically disordered proteins (IDPs) composed of sequences of low complexity (SLC) have been shown to serve a variety of important cellular functions, which include signalling, compartmentalization and stabilization. However, our understanding of these structures and our ability to synthesize models of them have been limited. We present design rules for IDPs possessing SLCs that phase separate into diverse assemblies within droplet microenvironments. Using theoretical analyses, we interpret the phase behaviour of archetypal IDP sequences and demonstrate the rational design of a vast library of multicomponent protein-rich structures that ranges from uniform nano-, meso- and microscale puncta (distinct protein droplets) to multilayered orthogonally phase-separated granular structures. The ability to predict and program IDP-rich assemblies in this fashion offers new insights into (1) genetic-to-molecular-to-macroscale relationships that encode hierarchical IDP assemblies, (2) design rules of such assemblies in cell biology and (3) molecular-level engineering of self-assembled recombinant IDP-rich materials.
富含蛋白质的动态细胞内结构包含由低复杂度序列（SLC）组成的相分离的固有无序蛋白质（IDP），这些结构具有多种重要的细胞功能，包括信号转导、区室化和稳定化。然而，我们对这些结构的理解以及合成它们的模型的能力受到了限制。我们提出了具有 SLC 的 IDP 的设计规则，这些 IDP 在液滴微环境中分离成不同的组装体。通过理论分析，我们解释了典型 IDP 序列的相行为，并展示了一个由多种成分组成的富含蛋白质的结构的合理设计，其范围从均匀的纳米、介观和微观点状（不同的蛋白质液滴）到多层正交相分离的颗粒结构。以这种方式预测和编程富含 IDP 的组装体的能力为（1）编码层次 IDP 组装的遗传-分子-宏观关系、（2）细胞生物学中此类组装的设计规则以及（3）自组装重组 IDP 丰富材料的分子水平工程提供了新的见解。
