Tethering-based chemogenetic approaches for the modulation of protein function in live cells.

Chemical Society Reviews
Yu-Hsuan TsaiShigeki Kiyonaka

Abstract

Proteins are the workhorse molecules performing various tasks to sustain life. To investigate the roles of a protein under physiological conditions, the rapid modulation of the protein with high specificity in a living system would be ideal, but achieving this is often challenging. To address this challenge, researchers have developed chemogenetic strategies for the rapid and selective modulation of protein function in live cells. Here, the target protein is modified genetically to become sensitive to a designer molecule that otherwise has no effect on other cellular biomolecules. One powerful chemogenetic strategy is to introduce a tethering point into the target protein, allowing covalent or non-covalent attachment of the designer molecule. In this tutorial review, we focus on tethering-based chemogenetic approaches for modulating protein function in live cells. We first describe genetic, optogenetic and chemical means to study protein function. These means lay the basis for the chemogenetic concept, which is explained in detail. The next section gives an overview, including advantages and limitations, of tethering tactics that have been employed for modulating cellular protein function. The third section provides examples of...Continue Reading

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Methods Mentioned

BETA
genetic modification
biosensors
transgenic

Software Mentioned

DART
GenoChemetics
BOLT

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