Reversible Control of Protein Localization in Living Cells Using a Photocaged-Photocleavable Chemical Dimerizer.

Reversible Control of Protein Localization in Living Cells Using a Photocaged-Photocleavable Chemical Dimerizer.
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使用光塑料 - 可透明的化学二聚体对活细胞中蛋白质定位的可逆控制。

DOI:
10.1021/jacs.8b07753
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发表时间:
2018-09-26
影响因子:
15
通讯作者:
Chenoweth DM
Chenoweth DM
中科院分区:
化学1区
文献类型:
--
作者:
Aonbangkhen C;Zhang H;Wu DZ;Lampson MA;Chenoweth DM

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许多动态的生物过程受蛋白质-蛋白质相互作用和蛋白质定位的调节。以时间和空间精度探测这种过程的实验技术包括可光激活蛋白质和化学诱导蛋白质二聚化(CID)。CID已被用于研究几个细胞事件,特别是细胞信号网络,这些事件通常是可逆的。然而,目前能够以高时空分辨率快速激活和失活的化学二聚体是有限的。在这里,我们提出了一种新型的蛋白质二聚化学诱导剂,它可以使用两个正交波长的单个光脉冲来快速开启和关闭。我们通过控制活细胞中的过氧化物体运输和有丝分裂检查点信号来证明该分子的实用性。我们的系统突出并增强了CID提供的时空控制。这个工具通过控制蛋白质之间的相互作用,在亚细胞水平上解决生物学问题。
Many dynamic biological processes are regulated by protein-protein interactions and protein localization. Experimental techniques to probe such processes with temporal and spatial precision include photoactivatable proteins and chemically-induced dimerization (CID) of proteins. CID has been used to study several cellular events, especially cell signaling networks, which are often reversible. However, chemical dimerizers that can be both rapidly activated and deactivated with high spatiotemporal resolution are currently limited. Herein, we present a novel chemical inducer of protein dimerization that can be rapidly turned on and off using single pulses of light at two orthogonal wavelengths. We demonstrate the utility of this molecule by controlling peroxisome transport and mitotic checkpoint signaling in living cells. Our system highlights and enhances the spatiotemporal control offered by CID. This tool addresses biological questions on sub-cellular levels by controlling protein-protein interactions.
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