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

Angew Chem Int Ed Engl. 2021 May 10;60(20):11378-11383. doi: 10.1002/anie.202016684. Epub 2021 Apr 6.

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.

Keywords: caged compound; dimerization; photochemistry; protein-protein interactions; proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Molecular Structure
  • Optical Phenomena
  • Photochemical Processes
  • Protein Binding
  • Protein Multimerization
  • Protein Transport
  • Proteins / chemistry*

Substances

  • Proteins