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A Chemically Disrupted Proximity System for Controlling Dynamic Cellular Processes.

ABSTRACT: Chemical methods that allow the spatial proximity of proteins to be temporally modulated are powerful tools for studying biology and engineering synthetic cellular behaviors. Here, we describe a new chemically controlled method for rapidly disrupting the interaction between two basally colocalized protein binding partners. Our chemically disrupted proximity (CDP) system is based on the interaction between the hepatitis C virus protease (HCVp) NS3a and a genetically encoded peptide inhibitor. Using clinically approved antiviral inhibitors as chemical disrupters of the NS3a/peptide interaction, we demonstrate that our CDP system can be used to confer temporal control over diverse intracellular processes. This NS3a-based CDP system represents a new modality for engineering chemical control over intracellular protein function that is complementary to currently available techniques.

SUBMITTER: Cunningham-Bryant D

PROVIDER: S-EPMC6492022 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A Chemically Disrupted Proximity System for Controlling Dynamic Cellular Processes.

Cunningham-Bryant Daniel D Dieter Emily M EM Foight Glenna W GW Rose John C JC Loutey Dana E DE Maly Dustin J DJ

Journal of the American Chemical Society 20190214 8

Chemical methods that allow the spatial proximity of proteins to be temporally modulated are powerful tools for studying biology and engineering synthetic cellular behaviors. Here, we describe a new chemically controlled method for rapidly disrupting the interaction between two basally colocalized protein binding partners. Our chemically disrupted proximity (CDP) system is based on the interaction between the hepatitis C virus protease (HCVp) NS3a and a genetically encoded peptide inhibitor. Usi ...[more]

PMID: 30735038

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