Optical Manipulation of Subcellular Protein Translocation Using a Photoactivatable Covalent Labeling System

The photoactivatable chemically induced dimerization (photo‐CID) technique for tag‐fused proteins is one of the most promising methods for regulating subcellular protein translocations and protein–protein interactions. However, light‐induced covalent protein dimerization in living cells has yet to b...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2021-05, Vol.60 (20), p.11378-11383
Main Authors: Kowada, Toshiyuki, Arai, Keisuke, Yoshimura, Akimasa, Matsui, Toshitaka, Kikuchi, Kazuya, Mizukami, Shin
Format: Article
Language:English
Subjects:
caged compound
Covalence
Cytoplasm
Dimerization
Labeling
Ligands
photochemistry
Protein interaction
Protein transport
Proteins
protein–protein interactions
Translocation
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Summary:The photoactivatable chemically induced dimerization (photo‐CID) technique for tag‐fused proteins is one of the most promising methods for regulating subcellular protein translocations and protein–protein interactions. However, light‐induced covalent protein dimerization in living cells has yet to be established, despite its various advantages. Herein, we developed a photoactivatable covalent protein‐labeling technology by applying a caged ligand to the BL‐tag system, a covalent protein labeling system that uses mutant β‐lactamase. We further developed CBHD, a caged protein dimerizer, using caged BL‐tag and HaloTag ligands, and achieved light‐induced protein translocation from the cytoplasm to subcellular regions. In addition, this covalent photo‐CID system enabled quick protein translocation to a laser‐illuminated microregion. These results indicate that the covalent photo‐CID system will expand the scope of CID applications in the optical manipulation of cellular functions. A photoactivatable chemically induced dimerization (photo‐CID) system based on covalent protein‐labeling technologies was developed by rationally designing a new caged ligand. This photo‐CID system enabled light‐induced protein translocation from the cytoplasm to subcellular regions such as the nucleus, mitochondrial outer membrane, and plasma membrane. Furthermore, quick protein translocation into a laser‐illuminated subcellular microregion was achieved.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202016684