Cell- Permeant and Photocleavable Chemical Inducer of Dimerization

被引：51

作者：

Zimmermann, Mirjam ^{[1
]}

Cal, Ruben ^{[1
]}

Janett, Elia ^{[2
]}

Hoffmann, Viktor ^{[1
]}

Bochet, Christian G. ^{[2
]}

Constable, Edwin ^{[3
]}

Beaufils, Florent ^{[1
]}

Wymann, Matthias P. ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, Basel, Switzerland

[2] Univ Fribourg, Dept Chem, CH-1700 Fribourg, Switzerland

[3] Univ Basel, Dept Chem, Basel, Switzerland

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2014年 / 53卷 / 18期

基金：

瑞士国家科学基金会;

关键词：

chemical inducers of dimerization; fusion proteins; photocleavable linkers; photolysis; protein-protein interactions; SPATIOTEMPORAL CONTROL; LIVING CELLS; PROTEIN INTERACTIONS; LIGHT; INDUCTION; MOLECULES; SWITCH;

D O I：

10.1002/anie.201310969

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Chemical inducers of dimerization (CIDs) have been developed to orchestrate protein dimerization and translocation. Here we present a novel photocleavable HaloTag- and SNAP-tag-reactive CID (MeNV-HaXS) with excellent selectivity and intracellular reactivity. Excitation at 360nm cleaves the methyl-6-nitroveratryl core of MeNV-HaXS. MeNV-HaXS covalently links HaloTag- and SNAP-tag fusion proteins, and enables targeting of selected membranes and intracellular organelles. MeNV-HaXS-mediated translocation has been validated for plasma membrane, late endosomes, lysosomes, Golgi, mitochondria, and the actin cytoskeleton. Photocleavage of MeNV-HaXS liberates target proteins and provides access to optical manipulation of protein relocation with high spatiotemporal and subcellular precision. MeNV-HaXS supports kinetic studies of protein dynamics and the manipulation of subcellular enzyme activities, which is exemplified for Golgi-targeted cargo and the assessment of nuclear import kinetics.

引用

页码：4717 / 4720

页数：4

共 26 条

[1]

[Anonymous], 2012, ANGEW CHEM INT ED, V51, P8446

[2]

[Anonymous], 2006, ANGEW CHEM INT ED, V45, P4900

[3]

[Anonymous], 2012, Angew. Chem

[4]

Castellano F, 2000, J CELL SCI, V113, P2955