Chemical Development of Intracellular Protein Heterodimerizers

被引：48

作者：

Erhart, Dominik ^{[1
]}

Zimmermann, Mirjam ^{[1
]}

Jacques, Olivier ^{[1
]}

Wittwer, Matthias B. ^{[2
]}

Ernst, Beat ^{[2
]}

Constable, Edwin ^{[3
]}

Zvelebil, Marketa ^{[4
]}

Beaufils, Florent ^{[1
]}

Wymann, Matthias P. ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, CH-4003 Basel, Switzerland

[2] Univ Basel, Dept Pharmaceut Sci, CH-4003 Basel, Switzerland

[3] Univ Basel, Dept Chem, CH-4003 Basel, Switzerland

[4] Inst Canc Res, London SW7 3RP, England

来源：

CHEMISTRY & BIOLOGY | 2013年 / 20卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

PHOSPHOINOSITIDE; 3-KINASE; SMALL MOLECULES; ACTIVATION; INDUCTION; CELLS; MECHANISMS; RAPAMYCIN; MTOR;

D O I：

10.1016/j.chembiol.2013.03.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cell activation initiated by receptor ligands or oncogenes triggers complex and convoluted intracellular signaling. Techniques initiating signals at defined starting points and cellular locations are attractive to elucidate the output of selected pathways. Here, we present the development and validation of a protein heterodimerization system based on small molecules cross-linking fusion proteins derived from Halo Tags and SNAP-tags. Chemical dimerizers of Halo Tag and SNAP-tag (HaXS) show excellent selectivity and have been optimized for intracellular reactivity. HaXS force protein-protein interactions and can translocate proteins to various cellular compartments. Due to the covalent nature of the HaloTag-HaXS-SNAP-tag complex, intracellular dimerization can be easily monitored. First applications include protein targeting to cytoskeleton, to the plasma membrane, to lysosomes, the initiation of the PI3K/mTOR pathway, and multiplexed protein complex formation in combination with the rapamycin dimerization system.

引用

页码：549 / 557

页数：9

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