Synthetic Self-Localizing Ligands That Control the Spatial Location of Proteins in Living Cells

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• 作者：Manabu Ishida ; Hideaki Watanabe ; Kazumasa Takigawa ; Yasutaka Kurishita ; Choji Oki ; Akinobu Nakamura ; Itaru Hamachi ; Shinya Tsukiji
• 刊名：Journal of the American Chemical Society
• 出版年：2013
• 出版时间：August 28, 2013
• 年：2013
• 卷：135
• 期：34
• 页码：12684-12689
• 全文大小：360K
• 年卷期：v.135,no.34(August 28, 2013)
• ISSN：1520-5126

文摘

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.