Optical Manipulation of Subcellular Protein Translocation Using a Photoactivatable Covalent Labeling System. Issue 20 (6th April 2021)

• Record Type: Journal Article
• Authors: Kowada, Toshiyuki; Arai, Keisuke; Yoshimura, Akimasa; Matsui, Toshitaka; Kikuchi, Kazuya; Mizukami, Shin
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 20(2021)
• Page Start: 11378
• Page End: 11383
• Publication Date: 2021-04-06
• Subjects: caged compound -- dimerization -- photochemistry -- protein–protein interactions -- proteins; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202016684
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : 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.