Synthetic Self-Localizing Ligands That Control the Spatial Location of Proteins in Living Cells
Synthetic Self-Localizing Ligands That Control the Spatial Location of Proteins in Living Cells
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DOI：
10.1021/ja4046907
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发表时间：
2013-08-28
影响因子：
15
通讯作者：
Tsukiji, Shinya
中科院分区：
文献类型：
--
作者：
Ishida, Manabu;Watanabe, Hideaki;Tsukiji, Shinya
控制活细胞中蛋白质空间位置的小分子配体将是调节生物系统的宝贵工具。然而，由于缺乏设计方法，这种分子的创造几乎尚未被探索。在这里，我们介绍了一种概念上新的合成配体，自定位配体（SLLs），它可以自发地定位到哺乳动物细胞的特定亚细胞区域。我们发现sll结合它们的靶蛋白并将它们快速地从细胞质转移到它们的靶位点，从而作为合成蛋白易位子。sll诱导的蛋白质易位使我们能够操纵多种合成/内源性信号通路。该方法也适用于可逆蛋白质易位，并允许在同一细胞的不同时间和位置控制多个蛋白质。这些结果证明了sll在细胞内蛋白质分布和生物过程的空间（和时间）控制中的有用性，为设计用于细胞调节的小分子工具或药物开辟了新的方向。
Small-molecule ligands that control the spatial location of proteins in living cells would be valuable tools for regulating biological systems. However, the creation of such molecules remains almost unexplored because of the lack of a design methodology. Here we introduce a conceptually new type of synthetic ligands, self-localizing ligands (SLLs), which spontaneously localize to specific subcellular regions in mammalian cells. We show that SLLs bind their target proteins and relocate (tether) them rapidly from the cytoplasm to their targeting sites, thus serving as synthetic protein translocators. SLL-induced protein translocation enables us to manipulate diverse synthetic/endogenous signaling pathways. The method is also applicable to reversible protein translocation and allows control of multiple proteins at different times and locations in the same cell. These results demonstrate the usefulness of SLLs in the spatial (and temporal) control of intracellular protein distribution and biological processes, opening a new direction in the design of small-molecule tools or drugs for cell regulation.