Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity.
Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity.
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DOI：
10.1038/nchem.2715
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发表时间：
2017-06
期刊：
影响因子：
21.8
通讯作者：
López GP
中科院分区：
文献类型：
--
作者：
Simon JR;Carroll NJ;Rubinstein M;Chilkoti A;López GP
动态富含蛋白质的细胞内结构含有由低复杂性序列 (SLC) 组成的相分离的本质无序蛋白 (IDP)，已被证明可以发挥多种重要的细胞功能，包括信号传导、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模型的能力是有限的。我们提出了具有 SLC 的 IDP 的设计规则，这些 SLC 在液滴微环境中相分离成不同的组件。通过理论分析，我们解释了原型 IDP 序列的相行为，并证明了一个庞大的富含多组分蛋白质结构库的合理设计，这些结构的范围从均匀的纳米、介观和微米尺度的点（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 的组件的能力为以下方面提供了新的见解：(1) 编码分层 IDP 组件的遗传到分子到宏观尺度的关系，(2) 细胞生物学中此类组件的设计规则，以及 (3) 自组装重组富含 IDP 材料的分子水平工程。现已开发出一种无膜细胞器的可编程模型，该模型由含有低复杂性序列的本质无序蛋白质（IDP）组成。控制原型 IDP 组装成受生物学启发的混合、分层和尺寸控制配置的规则为理解 IDP 的细胞内相行为提供了一种新方法。
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. A programmable model of membraneless organelles comprised of intrinsically disordered proteins (IDPs) containing sequences of low complexity has now been developed. The rules governing the assembly of archetypal IDPs into biologically inspired mixed-, layered- and size-controlled configurations provides a new means for understanding intracellular phase behaviour of IDPs.
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影响因子：
64.5
作者：
Feric M;Vaidya N;Harmon TS;Mitrea DM;Zhu L;Richardson TM;Kriwacki RW;Pappu RV;Brangwynne CP
通讯作者：
Brangwynne CP
影响因子：
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作者：
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影响因子：
16
作者：
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通讯作者：
Baldwin, Andrew J.
DOI：
10.1073/pnas.1504822112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Elbaum-Garfinkle, Shana;Kim, Younghoon;Brangwynne, Clifford P.
通讯作者：
Brangwynne, Clifford P.