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A Chemically Disrupted Proximity System for Controlling Dynamic Cellular Processes

Author:
Cunningham-Bryant, Daniel, Dieter, Emily M., Foight, Glenna W., Rose, John C., Loutey, Dana E., Maly, Dustin J.
Source:
Journal of the American Chemical Society 2019 v.141 no.8 pp. 3352-3355
ISSN:
1520-5126
Subject:
Hepatitis C virus, chemical control, engineering, peptides, proteinases, proteins
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.
Agid:
6323906