Intein Zymogens: Conditional Assembly and Splicing of Split Inteins via Targeted Proteolysis

Josef A. Gramespacher; Adam J. Stevens; Duy P. Nguyen; Jason W. Chin; Tom W. Muir

doi:10.1021/jacs.7b02618

Intein Zymogens: Conditional Assembly and Splicing of Split Inteins via Targeted Proteolysis

Josef A. Gramespacher, Adam J. Stevens, Duy P. Nguyen, Jason W. Chin, Tom W. Muir

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Naturally split inteins have found widespread use in chemical biology due to their ability to drive the ligation of separately expressed polypeptides through a process termed protein trans-splicing (PTS). In this study, we harness PTS by rendering association of split intein fragments conditional upon the presence of a user-defined protease. We show that these intein "zymogens" can be used to create protein sensors and actuators that respond to the presence of various stimuli, including bacterial pathogens, viral infections, and light. We also show that this design strategy is compatible with several orthogonal split intein pairs, thereby opening the way to the creation of multiplexed sensor systems.

Original language	English (US)
Pages (from-to)	8074-8077
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	139
Issue number	24
DOIs	https://doi.org/10.1021/jacs.7b02618
State	Published - Jun 21 2017

All Science Journal Classification (ASJC) codes

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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10.1021/jacs.7b02618

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AU - Chin, Jason W.

AU - Muir, Tom W.

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AB - Naturally split inteins have found widespread use in chemical biology due to their ability to drive the ligation of separately expressed polypeptides through a process termed protein trans-splicing (PTS). In this study, we harness PTS by rendering association of split intein fragments conditional upon the presence of a user-defined protease. We show that these intein "zymogens" can be used to create protein sensors and actuators that respond to the presence of various stimuli, including bacterial pathogens, viral infections, and light. We also show that this design strategy is compatible with several orthogonal split intein pairs, thereby opening the way to the creation of multiplexed sensor systems.

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Intein Zymogens: Conditional Assembly and Splicing of Split Inteins via Targeted Proteolysis

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