De novo engineering of intracellular condensates using artificial disordered proteins.

De novo engineering of intracellular condensates using artificial disordered proteins.
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DOI:
10.1038/s41557-020-0511-7
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发表时间:
2020-09
期刊:
影响因子:
21.8
通讯作者:
Chilkoti A
Chilkoti A
中科院分区:
化学1区
文献类型:
--
作者:
Dzuricky M;Rogers BA;Shahid A;Cremer PS;Chilkoti A

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内在无序蛋白质(IDP)的相分离是活细胞动态控制胞内分配的显著特征。尽管已经确定了许多新的IDP,但在细胞中进行合理工程的进展有限。为了解决这一限制,我们系统地扫描了天然IDP的序列空间,并设计了具有不同分子量和芳族含量的人工IDP(A-IDP),其在体外和细胞中表现出可变的冷凝物饱和浓度和温度浊点。我们使用这些简单的原理创建了A-IDP点,其能够螯合酶,并且其催化效率可以通过A-IDP的分子量来操纵。这些结果提供了一个强大的工程平台,用于在活细胞中产生具有新的相分离介导的生物功能控制的斑点。
Phase separation of intrinsically disordered proteins (IDPs) is a remarkable feature of living cells to dynamically control intracellular partitioning. Despite the numerous new IDPs that have been identified, progress towards rational engineering in cells has been limited. To address this limitation, we systematically scanned the sequence space of native IDPs and designed artificial IDPs (A-IDPs) with different molecular weights and aromatic content, which exhibit variable condensate saturation concentrations and temperature cloud points in vitro and in cells. We created A-IDP puncta using these simple principles, which are capable of sequestering an enzyme and whose catalytic efficiency can be manipulated by the molecular weight of the A-IDP. These results provide a robust engineered platform for creating puncta with new, phase-separation-mediated control of biological function in living cells.
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