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

TitleIntein Zymogens: Conditional Assembly and Splicing of Split Inteins via Targeted Proteolysis.
Publication TypeJournal Article
Year of Publication2017
AuthorsGramespacher, JA, Stevens, AJ, Nguyen, DP, Chin, JW, Muir, TW
JournalJ Am Chem Soc
Volume139
Issue24
Pagination8074-8077
Date Published2017 06 21
ISSN1520-5126
KeywordsEnzyme Precursors, Green Fluorescent Proteins, HEK293 Cells, Humans, Inteins, Peptides, Protein Splicing, Proteolysis
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.

DOI10.1021/jacs.7b02618
Alternate JournalJ. Am. Chem. Soc.
PubMed ID28562027
PubMed Central IDPMC5533455
Grant ListMC_U105181009 / / Medical Research Council / United Kingdom
R37 GM086868 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States