Proximity Induced Splicing Utilizing Caged Split Inteins.


Journal

Journal of the American Chemical Society
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056

Informations de publication

Date de publication:
04 09 2019
Historique:
pubmed: 17 8 2019
medline: 22 10 2020
entrez: 17 8 2019
Statut: ppublish

Résumé

Naturally split inteins drive the ligation of separately expressed polypeptides through a process called protein trans splicing (PTS). The ability to control PTS, so-called conditional protein splicing (CPS), has led to the development of tools to modulate protein structure and function at the post-translational level. CPS applications that utilize proximity as a trigger are especially intriguing as they afford the possibility to activate proteins in both a temporal and spatially targeted manner. In this study, we present the first proximity triggered CPS method that utilizes a naturally split fast splicing intein, Npu. We show that this method is amenable to diverse proximity triggers and capable of reconstituting and locally activating the acetyltransferase p300 in mammalian cells. This technology opens up a range of possibilities for the use of proximity triggered CPS.

Identifiants

pubmed: 31418547
doi: 10.1021/jacs.9b05721
pmc: PMC6903685
mid: NIHMS1054419
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13708-13712

Subventions

Organisme : NIGMS NIH HHS
ID : R37 GM086868
Pays : United States

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Auteurs

Josef A Gramespacher (JA)

Department of Chemistry , Princeton University , Frick Laboratory, Princeton , New Jersey 08544 , United States.

Antony J Burton (AJ)

Department of Chemistry , Princeton University , Frick Laboratory, Princeton , New Jersey 08544 , United States.

Luis F Guerra (LF)

Department of Chemistry , Princeton University , Frick Laboratory, Princeton , New Jersey 08544 , United States.

Tom W Muir (TW)

Department of Chemistry , Princeton University , Frick Laboratory, Princeton , New Jersey 08544 , United States.

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